Cancer Genetics Risk Assessment and Counseling (PDQ®)–Health Professional Version - National Cancer Institute

Cancer Genetics Risk Assessment and Counseling (PDQ®)–Health Professional Version - National Cancer Institute

Cancer Genetics Risk Assessment and Counseling (PDQ®)–Health Professional Version

Direct-to-Consumer (DTC) Genetic Tests

Most genetic testing for cancer and other health risks is offered by health care providers on the basis of a patient’s personal history, family history, or ethnicity. Increasingly, however, individuals can order genetic testing through DTC companies without the input of health care providers. DTC tests may provide information about ancestry, paternity, propensity toward certain physical traits, risk of adverse drug reactions, and disease risks.

Genotyping for carrier status and disease risks

In 2015, the FDA provided clearanceExit Disclaimer for a large DTC company (23andMe) to market carrier screening for Bloom syndrome, which is associated with increased cancer risks in homozygotes as well as other phenotypic features. Subsequently, DTC carrier testing for several conditions became available. In 2017, the FDA allowed 23andMe to market DTC tests for ten diseases or conditions including late-onset Alzheimer disease, Parkinson disease, and hereditary thrombophilia.[54] It is important to note that the carrier and health tests authorized for marketing by the FDA are performed by genotyping, which means that only specific nucleotides or bases are targeted for analysis; sequencing is not performed.[55] Thus, while the false-positive or false-negative rate for a specific genotype is very low (i.e., analytic validity is high), other pathogenic variants are not analyzed, nor is the entire sequence of the gene. Thus, the false-negative rate due to untested pathogenic variants as well as other gene abnormalities is high.

Genotyping for founder pathogenic variants in BRCA1 and BRCA2

In March 2018, the FDA authorized 23andMe to market DTC testing for three founder pathogenic variants in the BRCA1 and BRCA2 genes that are common in individuals of Ashkenazi Jewish descent.[56] These three variants are rare among high-risk individuals who are not of this ethnicity and in the general population of non-Jewish individuals. However, Jewish individuals whose family history is suggestive of hereditary breast/ovarian cancer who test negative for these three variants warrant additional testing.

It is crucial for individuals who obtain a BRCA1/BRCA2 (or any health-related) positive result from DTC testing to pursue clinical confirmation of such a result. Clinical confirmation entails repeating the test in a CLIA-certified lab, as well as individual review and verification of the result by laboratory personnel.

A potential advantage of DTC testing of these three BRCA1/BRCA2 pathogenic variants is that it will identify individuals who would not have been otherwise aware of their increased risk of associated cancers, for example if they have no personal or family history of breast, ovarian, or prostate cancer. This is one of the main arguments for population-based screening for BRCA1/BRCA2 pathogenic variants. (Refer to the Population screening section in the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information.)

However, a negative result does not rule out other hereditary factors or account for other clinical indicators, genetic and nongenetic, of increased cancer risk. Thus, for most individuals who test negative for the three BRCA1/BRCA2 variants, the results do not provide reassurance about their cancer risks. For high-risk individuals in particular (i.e., those with a history suggestive of hereditary breast/ovarian cancer) a negative result from this limited testing is incomplete, given that it does not assess the presence or absence of other pathogenic variants in BRCA1/BRCA2 or in many other cancer-associated genes.

Testing for SNPs

In the past, several DTC companies offered only single nucleotide polymorphism (SNP)-based testing to generate information about health risks, including risks of cancer. Selection of SNPs may be based on data from genome-wide association studies (GWAS); however, there is no validated algorithm outlining how to generate cancer risk estimates from different SNPs, which individually are generally associated with modestly increased disease risks (usually conferring odds ratios <2.0) or modestly decreased disease risks.[57] (Refer to the GWAS section in the Cancer Genetics Overview PDQ summary for more information.) As a result, predicted disease risks from different DTC companies may yield different results. For example, a sample comparison of SNP-based risk prediction from two different companies for four different cancers yielded relative risks of 0.64 to 1.42 (excluding the three Ashkenazi BRCA1/BRCA2 founder pathogenic variants).[58] In addition, because commercial companies use different panels of SNPs, there is seldom concordance about the predicted risks for common diseases, and such risk estimates have not been prospectively validated.[59,60]

Another area of investigation is whether predicted disease risks from SNP testing are consistent with family history–based assessments. Studies using data from one commercial personal genomic testing company revealed that there was generally poor concordance between the SNP and family history risk assessment for common cancers such as breast, prostate, and colon.[61-63] Importantly, one of these studies highlighted that the majority of individuals with family histories suggestive of hereditary breast/ovarian cancer or Lynch syndrome received SNP results yielding lifetime cancer risks that were average or below average.[61]

Studies have begun to examine whether SNP testing could be used together with other established risk factors to assess the likelihood of developing cancer. For example, adding SNP data to validated breast cancer prediction tools such as those included in the National Cancer Institute's Breast Cancer Risk Assessment Tool (based on the Gail model) [64] may improve the accuracy of risk assessment.[65,66] However, this approach is not currently FDA-approved.

These findings underscore that SNP testing has not been validated as an accurate risk assessment tool and does not replace the collection, integration, and interpretation of personal and family history risk factor information by qualified health care professionals.

DTC whole-exome/genome sequencing and interpretation

Increasingly, DTC testing companies offer whole-genome sequencing (WGS) or whole-exome sequencing (WES), including SNP data. (Refer to the Clinical Sequencing section in the Cancer Genetics Overview PDQ summary for a description of WGS and WES.) In addition, consumers who submit their DNA to a DTC lab may have access to their raw sequence data and may consult with other companies, websites, and open-access databases for interpretation.[67,68] However, these data must be interpreted with caution. A clinical lab found that 40% of variants reported in DTC raw data were false positives (i.e., low analytic validity because the identified variant was not present).[69] In addition, several variants that were designated as “increased risk” in the raw data were classified as benign by clinical laboratories and public databases.[69] Given the potential for misinterpretation, which may lead to unnecessary medical procedures or testing, these findings underscore the importance of clinical confirmation of all potentially medically actionable gene variants identified by DTC testing.

Some factors to consider when determining the accuracy and utility of sequence data for cancer (or other disease) risk assessment include the sequencing depth of the genes of interest, whether large rearrangements or gene deletions would be detected, and whether or how positive results are confirmed (e.g., through Sanger sequencing). For example, if sequencing depth is low or rare variants cannot be detected, then there is a concern about false-negative results. There is also a risk that sequence changes will be erroneously labeled as pathogenic when confirmatory testing or different interpretative approaches would determine that the variant identified is benign (false positive). When WES or WGS is performed, VUS are also likely to be identified,[70] and DTC companies have varying protocols for classification, which may or may not be consistent with national guidelines (e.g., refer to [71]). In addition, as evidence evolves and variants are reclassified, consumers need to be aware of the process the DTC lab has, if any, for updating information and re-contacting consumers with revised interpretations.

Considerations

There may be potential benefits associated with DTC testing. DTC marketing and provision of genetic tests may promote patient autonomy.[58] Individuals may develop an increased awareness of the importance of family history, the relationship between risk and family history, the role of genetics in disease, and a better understanding of the value of genetic counseling.[72] Although results of SNP-based DTC testing appear to motivate some individuals to seek the advice of their doctor, make lifestyle changes, and pursue screening tests,[73-76] short-term modest effects on risk perception after notification of an elevated risk (e.g., for cancer) may not significantly alter lifestyle or cancer screening behaviors.[77,78] Further, psychological distress has not been widely reported among consumers who have undergone DTC testing for a variety of conditions.[75] However, little is known about how individuals respond after learning that they carry pathogenic variants in high-risk genes such as BRCA1/BRCA2 when testing is performed within a DTC context and without traditional forms of pre- and posttest genetic education and counseling.

Given the complexity of genomic testing, several professional organizations have released position statements about DTC genetic testing. For example, in 2010, ASCO published a position statement outlining several considerations related to DTC cancer genomic tests, including those mentioned above.[1] They endorsed pre- and posttest genetic counseling and informed consent by qualified health care professionals. ASCO’s 2015 position statement on genetic and genomic testing for cancer susceptibility reinforces the importance of provider education given the complexity of genomic testing and interpretation and discusses their recommendations for regulatory review of genomic tests, including those offered by DTC companies.[2]

In 2016, a statement by the American College of Medical Genetics and Genomics about DTC genetic testing similarly endorsed the involvement of qualified genetics professionals in the processes of test ordering and interpretation.[79] The statement also emphasized the need to incorporate established methods of risk assessment into disease risk prediction (such as personal and family medical history information) and stressed that consumers need to be informed about the potential limitations and risks associated with DTC testing.

Informed Consent

Informed consent can enhance preparedness for testing, including careful weighing of benefits and limitations of testing, minimization of adverse psychosocial outcomes, appropriate use of medical options, and a strengthened provider-patient relationship based on honesty, support, and trust.

Consensus exists among experts that a process of informed consent should be an integral part of the pretest counseling process.[80] This view is driven by several ethical dilemmas that can arise in genetic susceptibility testing. The most commonly cited concern is the possibility of insurance or employment discrimination if a test result, or even the fact that an individual has sought or is seeking testing, is disclosed. In 2008, Congress passed the Genetic Information Nondiscrimination Act (GINA). This federal law provides protections related to health insurance and employment discrimination based on genetic information. However, GINA does not cover life, disability, or long-term-care insurance discrimination.[81] A related issue involves stigmatization that may occur when an individual who may never develop the condition in question, or may not do so for decades, receives genetic information and is labeled or labels himself or herself as ill. Finally, in the case of genetic testing, medical information given to one individual has immediate implications for biologic relatives. These implications include not only the medical risks but also disruptions in familial relationships. The possibility for coercion exists when one family member wants to be tested but, to do so optimally, must first obtain genetic material or information from other family members.

Inclusion of an informed consent process in counseling can facilitate patient autonomy.[82] It may also reduce the potential for misunderstanding between patient and provider. Many clinical programs provide opportunities for individuals to review their informed consent during the genetic testing and counseling process. Initial informed consent provides a verbal and/or written overview of the process.

Some programs use a second informed consent process prior to disclosure to the individual of his or her genetic test results. This process allows for the possibility that a person may change his or her mind about receiving test results. After the test result has been disclosed, a third informed consent discussion often occurs. This discussion concerns issues regarding sharing the genetic test result with health providers and/or interested family members, currently or in the future. Obtaining written permission to provide the test result to others in the family who are at risk can avoid vexing problems in the future should the individual not be available to release his or her results.

Core elements of informed consent

Major elements of an informed consent discussion are highlighted in the preceding discussion. The critical elements, as described in the literature,[1,2,83,84] include the following:

• Elicitation and discussion of a person’s expectations, beliefs, goals, and motivations.
• Explanation of how inheritance of genetic factors may affect cancer susceptibility.
• Clarification of a person’s increased risk status.
• Discussion of potential benefits, risks, and limitations of testing.
• Discussion of costs and logistics of testing and follow-up.
• Discussion of possible outcomes of testing (e.g., true positive, true negative, VUS, inconclusive, false positive, false negative).
• Discussion of medical management options based on risk assessment and/or test results available for those who choose to test, for those who choose not to test, and for those who have positive, negative, or inconclusive results.
• Data on efficacy of methods of cancer prevention and early detection.
• Discussion of possible psychological, social, economic, and family dynamic ramifications of testing or not testing.
• Discussion of alternatives to genetic testing (e.g., tissue banking, risk assessment without genetic testing).
• Attainment of verbal and written informed consent or clarification of the decision to decline testing.

All individuals considering genetic testing should be informed that they have several options even after the genetic testing has been completed. They may decide to receive the results at the posttest meeting, delay result notification, or less commonly, not receive the results of testing. They should be informed that their interest in receiving results will be addressed at the beginning of the posttest meeting and that time will be available to review their concerns and thoughts on notification. It is important that individuals receive this information during the pretest counseling to ensure added comfort with the decision to decline or defer result notification even when test results become available.

Testing in children

Genetic testing for pathogenic variants in cancer susceptibility genes in children is particularly complex. While both parents [85] and providers [86] may request or recommend testing for minor children, many experts recommend that unless there is evidence that the test result will influence the medical management of the child or adolescent, genetic testing should be deferred until legal adulthood (age 18 y or older) because of concerns about autonomy, potential discrimination, and possible psychosocial effects.[87-89] A number of cancer syndromes include childhood disease risk, such as retinoblastoma, multiple endocrine neoplasia (MEN) types 1 and 2 (MEN1 and MEN2), neurofibromatosis types 1 and 2 (NF1 and NF2), Beckwith–Wiedemann syndrome, Fanconi anemia, FAP, and Von Hippel-Lindau disease (VHL).[90,91] As a consequence, decisions about genetic testing in children are made in the context of a specific gene in which a pathogenic variant is suspected. The ASCO statement on genetic testing for cancer susceptibility maintains that the decision to consider offering childhood genetic testing should take into account not only the risk of childhood malignancy but also the evidence associated with risk reduction interventions for that disorder.[1] Specifically, ASCO recommends that:

• When screening or preventive strategies during childhood are available (e.g., MEN and FAP), testing should be encouraged on clinical grounds.
• When no risk reduction strategies are available in childhood and the probability of developing a malignancy during childhood is very low (e.g., hereditary breast/ovarian cancer syndrome), testing should not be offered.
• Some patients may be at risk of developing a malignancy during childhood without the availability of validated risk-reduction strategies (e.g., TP53 pathogenic variants). The decision to test in such circumstances is particularly controversial.[1]

Special considerations are required when genetic counseling and testing for pathogenic variants in cancer susceptibility genes are considered in children. The first issue is the age of the child. Young children, especially those younger than 10 years, may not be involved or may have limited involvement in the decision to be tested, and some may not participate in the genetic counseling process. In these cases, the child’s parents or other legal surrogate will be involved in the genetic counseling and will ultimately be responsible for making the decision to proceed with testing.[1,92] Counseling under these circumstances incorporates a discussion of how test results will be shared with the child when he or she is older.[1] Children aged 10 to 17 years may have more involvement in the decision-making process.[93] In a qualitative study of parents and children aged 10 to 17 years assessing decision making for genetic research participation, older, more mature children and families with open communication styles were more likely to have joint decision making. The majority of children in this study felt that they should have the right to make the final decision for genetic research participation, although many would seek input from their parents.[93] While this study is specific to genetic research participation, the findings allude to the importance children aged 10 to 17 years place on personal decision making regarding factors that impact them. Unfortunately cognitive and psychosocial development may not consistently correlate with the age of the child.[92] Therefore, careful assessment of the child’s developmental stage may help in the genetic counseling and testing process to facilitate parent and child adaptation to the test results. Another complicating factor includes potential risks for discrimination. (Refer to the Employment and Insurance Discrimination section in the Ethical, Legal, and Social Implications section of this summary for more information.)

The consequences of genetic testing in children have been reviewed.[92] In contrast to observations in adults, young children in particular are vulnerable to changes in parent and child bonding based on test results. Genetic testing could interfere with the development of self-concept and self-esteem. Children may also be at risk of developing feelings of survivor guilt or heightened anxiety. All children are especially susceptible to not understanding the testing, results, or implications for their health. As children mature, they begin to have decreased dependency on their parents while developing their personal identity. This can be altered in the setting of a serious health condition or an inherited disorder. Older children are beginning to mature physically and develop intimate relationships while also changing their idealized view of their parents. All of this can be influenced by the results of a genetic test.[92] In its recommendations for genetic testing in asymptomatic minors, the European Society of Human Genetics emphasizes that parents have a responsibility to inform their children about their genetic risk and to communicate this information in a way that is tailored to the child’s age and developmental level.[94,95]

In summary, the decision to proceed with testing in children is based on the use of the test for medical decision making for the child, the ability to interpret the test, and evidence that changes in medical decision making in childhood can positively impact health outcomes. Deferral of genetic testing is suggested when the risk of childhood malignancy is low or absent and/or there is no evidence that interventions can reduce risk.[1] When offering genetic testing in childhood, consideration of the child’s developmental stage is used to help determine his or her involvement in the testing decision and who has legal authority to provide consent. In addition, careful attention to intrafamilial issues and potential psychosocial consequences of testing in children can enable the provider to deliver support that facilitates adaptation to the test result. (Refer to the PDQ summaries on Genetics of Breast and Gynecologic Cancers; Genetics of Colorectal Cancer; and Genetics of Endocrine and Neuroendocrine Neoplasias for more information about psychosocial research in children being tested for specific cancer susceptibility gene pathogenic variants.)

Testing in vulnerable populations

Genetic counseling and testing requires special considerations when used in vulnerable populations. In 1995, the American Society of Human Genetics published a position statement on the ethical, legal, and psychosocial implications of genetic testing in children and adolescents as a vulnerable population.[88] However, vulnerable populations encompass more than just children. Federal policy applicable to research involving human subjects, 45 CFR Code of Federal Regulations part 46 Protection Of Human Subjects, considers the following groups as potentially vulnerable populations: prisoners, traumatized and comatose patients, terminally ill patients, elderly/aged persons who are cognitively impaired and/or institutionalized, minorities, students, employees, and individuals from outside the United States. Specific to genetic testing, the International Society of Nurses in GeneticsExit Disclaimer further expanded the definition of vulnerable populations to also include individuals with hearing and language deficits or conditions limiting communication (for example, language differences and concerns with reliable translation), cognitive impairment, psychiatric disturbances, clients undergoing stress due to a family situation, those without financial resources, clients with acute or chronic illness and in end-of-life, and those in whom medication may impair reasoning.

Genetic counseling and testing in vulnerable populations raises special considerations. The aim of genetic counseling is to help people understand and adapt to the medical, psychological, and familial implications of genetic contributions to disease, which in part involves the meaningful exchange of factual information.[96] In a vulnerable population, health care providers need to be sensitive to factors that can impact the ability of the individual to comprehend the information. In particular, in circumstances of cognitive impairment or intellectual disability, special attention is paid to whether the individual’s legally authorized representative should be involved in the counseling, informed consent, and testing process.

Providers need to assess all patients for their ability to make an uncoerced, autonomous, informed decision prior to proceeding with genetic testing. Populations that do not seem vulnerable (e.g., legally adult college students) may actually be deemed vulnerable because of undue coercion for testing by their parents or the threat of withholding financial support by their parents based on a testing decision inconsistent with the parent’s wishes. Alteration of the genetic counseling and testing process may be necessary depending on the situation, such as counseling and testing in terminally ill individuals who opt for testing for the benefit of their children, but given their impending death, results may have no impact on their own health care or may not be available before their death. In summary, genetic counseling and testing requires that the health care provider assess all individuals for any evidence of vulnerability, and if present, be sensitive to those issues, modify genetic counseling based on the specific circumstances, and avoid causing additional harm.

Importance of Pretest Counseling

The complexity of genetic testing for cancer susceptibility has led experts to suggest that careful, in-depth counseling should precede any decision about the use of testing, in keeping with the accepted principles for the use of genetic testing.[97]

Qualitative and quantitative research studies indicate that families hold a variety of beliefs about the inheritance of characteristics within families; some of these beliefs are congruent with current scientific understanding, whereas others are not.[98-100] These beliefs may be influenced by education, personal and family experiences, and cultural background. Because behavior is likely to be influenced by these beliefs, the usefulness of genetic information may depend on recognizing and addressing the individual’s preexisting cognitions. This process begins with initial discussion and continues throughout the genetic counseling process.

Psychological Impact of Genetic Information/Test Results on the Individual

An accurate assessment of psychosocial functioning and emotional factors related to testing motivation and potential impact and utilization is an important part of pretest counseling.[101-105] Generally, a provider inquires about a person’s emotional response to the family history of cancer and also about a person’s response to his or her own risk of developing cancer. People have various coping strategies for dealing with stressful circumstances such as genetic risk. Identifying these strategies and ascertaining how well or poorly they work will have implications for the support necessary during posttest counseling and will help personalize the discussion of anticipated risks and benefits of testing. Taking a brief history of past and current psychiatric symptoms (e.g., depression, extreme anxiety, or suicidality) will allow for an assessment of whether this individual is at particular risk of adverse effects after disclosure of results. In such cases, further psychological assessment may be indicated.

In addition, cognitive deficits in the person being counseled may significantly limit understanding of the genetic information provided and hinder the ability to give informed consent and may also require further psychological assessment. Emotional responses to cancer risk may also affect overall mood and functioning in other areas of life such as home, work, and personal health management, including cancer screening practices.[106] Education and genetic counseling sessions provide an ongoing opportunity for informal assessment of affective and cognitive aspects of the communication process. Since behavioral factors influence adherence to screening and surveillance recommendations, consideration of emotional barriers is important in helping a person choose prevention strategies and in discussing the potential utility of genetic testing.[107,108]

The discussion of issues such as history of depression, anxiety, and suicidal thoughts or tendencies requires sensitivity to the individual. The individual must be assured that the counseling process is a collaborative effort to minimize intrusiveness while maximizing benefits. Determining whether the individual is currently receiving treatment for major psychiatric illness is an important part of the counseling process. Consultation with a mental health professional familiar with psychological assessments may be useful to help the provider develop the strategies for these discussions. It also may be beneficial for the individual to be given standard psychological self-report instruments that assess levels of depression, anxiety, and other psychiatric difficulties that he or she may be experiencing. This step provides objective comparisons with already established normative data.[109,110]

In addition to the clinical assessment of psychological functioning, several instruments for cancer patients and people at increased risk of cancer have been utilized to assess psychological status. These include the Center for Epidemiological Studies-Depression scale,[111] the Profile of Mood States,[112] the Hospital Anxiety and Depression Scale,[113] and the Brief Symptom Inventory.[114] Research programs have included one or more of these instruments as a way of helping refine the selection of people at increased risk of adverse psychosocial consequences of genetic testing. Psychological assessments are an ongoing part of genetic counseling. Some individuals with symptoms of increased distress, extreme avoidance of affect, or other marked psychiatric symptoms may benefit from a discussion with, or evaluation by, a mental health professional. It may be suggested to some people (generally, a very small percentage of any population) that testing be postponed until greater emotional stability has been established.

Psychological Impact of Genetic Information/Test Results on the Family

In addition to making an assessment of the family history of cancer, the family as a social system may also be assessed as part of the process of cancer genetic counseling. Hereditary susceptibility to cancer may affect social interactions and attitudes toward the family.[115]

In assessing families, characteristics that may be relevant are the organization of the family (including recognition of individuals who propose to speak for or motivate other family members), patterns of communication within the family, cohesion or closeness of family members (or lack thereof), and the family beliefs and values that affect health behaviors. Ethnocultural factors may also play an important role in guiding behavior in some families.

Assessment also evaluates the impact of the family’s prior experience with illness on their attitudes and behaviors related to genetic counseling and testing. Prior experience with cancer diagnosis and treatment, loss due to cancer, and the family members’ interaction with the medical community may heavily influence attitudes toward receiving genetic information and may play a major role in the emotional state of individuals presenting for genetic services.

The practitioner may use the above framework to guide inquiries about the relationship of the individual to (1) the affected members of the family or (2) others who are considering or deciding against the consideration of genetic counseling or testing. Inquiries about how the family shares (or does not share) information about health, illness, and genetic susceptibility may establish whether the individual feels under pressure from other family members or anticipates difficulty in sharing genetic information obtained from counseling or testing. Inquiries about the present health (new diagnoses or deaths from cancer) or relationship status (divorce, marriage, grieving) of family members may inform the provider about the timing of the individual’s participation in counseling or testing and may also reveal possible contraindications for testing at present.

Evidence from a study of 297 persons from 38 Lynch syndrome–affected families suggested that the timing of genetic counseling and testing services may influence psychological test-related distress responses. Specifically, family members in the same generation as the index case were more likely to experience greater test-related distress with increasingly longer lengths of time between the index case's receipt of MMR pathogenic variant results and the provision of genetic counseling and testing services to family members. However, it was unclear whether time lapses were due to a delay in the index case communicating test results or the family member choosing to delay genetic testing, despite being aware of the index case’s results.[116]

More specific information about family functioning in coping with hereditary cancers can be found in the psychosocial or counseling sections of PDQ summaries on the genetics of specific types of cancer. (Refer to the PDQ summaries on Genetics of Breast and Gynecologic Cancers and Genetics of Colorectal Cancer for more information.)

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61. Aiyar L, Shuman C, Hayeems R, et al.: Risk estimates for complex disorders: comparing personal genome testing and family history. Genet Med 16 (3): 231-7, 2014. [PUBMED Abstract]
62. Heald B, Edelman E, Eng C: Prospective comparison of family medical history with personal genome screening for risk assessment of common cancers. Eur J Hum Genet 20 (5): 547-51, 2012. [PUBMED Abstract]
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65. McCarthy AM, Armstrong K, Handorf E, et al.: Incremental impact of breast cancer SNP panel on risk classification in a screening population of white and African American women. Breast Cancer Res Treat 138 (3): 889-98, 2013. [PUBMED Abstract]
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67. Glusman G, Cariaso M, Jimenez R, et al.: Low budget analysis of Direct-To-Consumer genomic testing familial data. F1000Res 1: 3, 2012. [PUBMED Abstract]
68. Cariaso M, Lennon G: SNPedia: a wiki supporting personal genome annotation, interpretation and analysis. Nucleic Acids Res 40 (Database issue): D1308-12, 2012. [PUBMED Abstract]
69. Tandy-Connor S, Guiltinan J, Krempely K, et al.: False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med 20 (12): 1515-1521, 2018. [PUBMED Abstract]
70. Berg JS, Khoury MJ, Evans JP: Deploying whole genome sequencing in clinical practice and public health: meeting the challenge one bin at a time. Genet Med 13 (6): 499-504, 2011. [PUBMED Abstract]
71. Richards S, Aziz N, Bale S, et al.: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17 (5): 405-24, 2015. [PUBMED Abstract]
72. McCabe LL, McCabe ER: Direct-to-consumer genetic testing: access and marketing. Genet Med 6 (1): 58-9, 2004 Jan-Feb. [PUBMED Abstract]
73. Bansback N, Sizto S, Guh D, et al.: The effect of direct-to-consumer genetic tests on anticipated affect and health-seeking behaviors: a pilot survey. Genet Test Mol Biomarkers 16 (10): 1165-71, 2012. [PUBMED Abstract]
74. Kaufman DJ, Bollinger JM, Dvoskin RL, et al.: Risky business: risk perception and the use of medical services among customers of DTC personal genetic testing. J Genet Couns 21 (3): 413-22, 2012. [PUBMED Abstract]
75. Bloss CS, Schork NJ, Topol EJ: Effect of direct-to-consumer genomewide profiling to assess disease risk. N Engl J Med 364 (6): 524-34, 2011. [PUBMED Abstract]
76. van der Wouden CH, Carere DA, Maitland-van der Zee AH, et al.: Consumer Perceptions of Interactions With Primary Care Providers After Direct-to-Consumer Personal Genomic Testing. Ann Intern Med 164 (8): 513-22, 2016. [PUBMED Abstract]
77. Carere DA, VanderWeele T, Moreno TA, et al.: The impact of direct-to-consumer personal genomic testing on perceived risk of breast, prostate, colorectal, and lung cancer: findings from the PGen study. BMC Med Genomics 8: 63, 2015. [PUBMED Abstract]
78. Gray SW, Gollust SE, Carere DA, et al.: Personal Genomic Testing for Cancer Risk: Results From the Impact of Personal Genomics Study. J Clin Oncol 35 (6): 636-644, 2017. [PUBMED Abstract]
79. ACMG Board of Directors: Direct-to-consumer genetic testing: a revised position statement of the American College of Medical Genetics and Genomics. Genet Med 18 (2): 207-8, 2016. [PUBMED Abstract]
80. Geller G, Botkin JR, Green MJ, et al.: Genetic testing for susceptibility to adult-onset cancer. The process and content of informed consent. JAMA 277 (18): 1467-74, 1997. [PUBMED Abstract]
81. Hudson KL, Holohan MK, Collins FS: Keeping pace with the times--the Genetic Information Nondiscrimination Act of 2008. N Engl J Med 358 (25): 2661-3, 2008. [PUBMED Abstract]
82. Geller G, Doksum T, Bernhardt BA, et al.: Participation in breast cancer susceptibility testing protocols: influence of recruitment source, altruism, and family involvement on women's decisions. Cancer Epidemiol Biomarkers Prev 8 (4 Pt 2): 377-83, 1999. [PUBMED Abstract]
83. American College of Medical Genetics: Genetic susceptibility to breast and ovarian cancer: assessment, counseling and testing guidelines. New York: New York State Department of Health, American College of Medical Genetics Foundation, 1999.
84. McKinnon WC, Baty BJ, Bennett RL, et al.: Predisposition genetic testing for late-onset disorders in adults. A position paper of the National Society of Genetic Counselors. JAMA 278 (15): 1217-20, 1997. [PUBMED Abstract]
85. Bradbury AR, Patrick-Miller L, Egleston B, et al.: Parent opinions regarding the genetic testing of minors for BRCA1/2. J Clin Oncol 28 (21): 3498-505, 2010. [PUBMED Abstract]
86. O'Neill SC, Peshkin BN, Luta G, et al.: Primary care providers' willingness to recommend BRCA1/2 testing to adolescents. Fam Cancer 9 (1): 43-50, 2010. [PUBMED Abstract]
87. Nelson RM, Botkjin JR, Kodish ED, et al.: Ethical issues with genetic testing in pediatrics. Pediatrics 107 (6): 1451-5, 2001. [PUBMED Abstract]
88. Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. American Society of Human Genetics Board of Directors, American College of Medical Genetics Board of Directors. Am J Hum Genet 57 (5): 1233-41, 1995. [PUBMED Abstract]
89. Wertz DC, Fanos JH, Reilly PR: Genetic testing for children and adolescents. Who decides? JAMA 272 (11): 875-81, 1994. [PUBMED Abstract]
90. Field M, Shanley S, Kirk J: Inherited cancer susceptibility syndromes in paediatric practice. J Paediatr Child Health 43 (4): 219-29, 2007. [PUBMED Abstract]
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93. Bernhardt BA, Tambor ES, Fraser G, et al.: Parents' and children's attitudes toward the enrollment of minors in genetic susceptibility research: implications for informed consent. Am J Med Genet A 116 (4): 315-23, 2003. [PUBMED Abstract]
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95. Borry P, Evers-Kiebooms G, Cornel MC, et al.: Genetic testing in asymptomatic minors: background considerations towards ESHG Recommendations. Eur J Hum Genet 17 (6): 711-9, 2009. [PUBMED Abstract]
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98. Tessaro I, Borstelmann N, Regan K, et al.: Genetic testing for susceptibility to breast cancer: findings from women's focus groups. J Womens Health 6 (3): 317-27, 1997. [PUBMED Abstract]
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Education and Counseling About Risk/Risk Communication

In This Section

• Methods of Risk Presentation
• Risk Communication
• Communication Strategies

Specific clinical programs for risk management may be offered to persons with an increased genetic risk of cancer. These programs may differ from those offered to persons of average risk in several ways: screening may be initiated at an earlier age or involve shorter screening intervals; screening strategies not in routine use, such as screening for ovarian cancer, may be offered; and interventions to reduce cancer risk, such as risk-reducing surgery, may be offered. Current recommendations are summarized in the PDQ summaries addressing the genetics of specific cancers.

The goal of genetic education and counseling is to help individuals understand their personal risk status, their options for cancer risk management, and to explore feelings regarding their personal risk status. Counseling focuses on obtaining and giving information, promoting autonomous decision making, and facilitating informed consent if genetic testing is pursued.

Optimally, education and counseling about cancer risk includes providing the following information:

• Purpose, strengths, and limitations of cancer risk assessment.
• Basic genetics and patterns of inheritance.
• Genetic basis of cancer.
• Clinical features of relevant hereditary cancer syndromes.
• Evidence of a hereditary cancer syndrome from the consultand's personal and family history.
• Options for clarifying cancer risk, including genetic testing, if indicated.
• Options available for risk management, including data (or lack of data) on the efficacy of different measures for early detection and risk reduction.
• Signs and symptoms of cancer.

When a clinically valid genetic test is available, education and counseling for genetic testing typically includes the following:

• Risk of having a pathogenic variant and patterns of transmission.
• Alternatives to genetic testing.
• Risks, benefits and limitations of genetic testing, including psychological and discriminatory risks.
• Possible test outcomes, including likelihood of uninformative results and identifying variants of uncertain significance.
• Sensitivity of the genetic test, including the techniques utilized to perform the test and their associated limitations.
• Health care management options based on possible test results.
• Implications for children and other family members based on pattern of transmission.
• Dissemination of risk and genetic information to family members.
• Cost associated with testing, counseling, medical management, and options for insurance coverage.
• How genetic information and genetic test results will be recorded in the medical record.
• Specimen storage and reuse, if applicable.

If a second session is held to disclose and interpret genetic test results, education and counseling focuses on the following:

• Interpretation of test results.
• Discussion of further testing that may clarify risk (e.g., large rearrangement testing and testing the other genes based on the patient's differential cancer syndrome list).
• Assessment of the emotional and behavioral responses to genetic test results.
• Recommendations for coping and communication strategies to address issues related to cancer risk.
• Cancer risk management recommendations.
• Risk analysis and dissemination of risk results to family members.

The process of counseling may require more than one visit to address medical, genetic testing, and psychosocial support issues. Additional case-related preparation time is spent before and after the consultation sessions to obtain and review medical records, complete case documentation, seek information about differential diagnoses, identify appropriate laboratories for genetic tests, find patient support groups, research resources, and communicate with or refer to other specialists.[1]

Information about inherited risk of cancer is growing rapidly. Many of the issues discussed in a counseling session may need to be revisited as new information emerges. At the end of the counseling process, individuals are typically reminded of the possibility that future research may provide new options and/or new information on risk. Individuals may be advised to check in with the health care provider periodically to determine whether new information is sufficient to merit an additional counseling session. The obligation of health care providers to recontact individuals when new genetic testing or treatment options are available is controversial, and standards have not been established.

Methods of Risk Presentation

The usage of numerical probabilities to communicate risk may overestimate the level of risk certainty, especially when wide confidence intervals exist to the estimates or when the individual may differ in important ways from the sample on which the risk estimate was derived. Also, numbers are often inadequate for expressing gut-level or emotional aspects of risk. Finally, there are wide variations in individuals’ level of understanding of mathematical concepts (i.e., numeracy). For all the above reasons, conveying risk in multiple ways, both numerically and verbally, with discussion of important caveats, may be a useful strategy to increase risk comprehension. The numerical format that facilitates the best understanding is natural frequencies because frequencies include information concerning the denominator, the reference group to which the individual may refer. In general, logarithmic scales are to be avoided.[2] Additionally, important “contextual” risks may be included with the frequency in order to increase risk comprehension; these may include how the person’s risk compares with those who do not have the risk factor in question and the risks associated with common hazards, such as being in a car accident. Additional suggestions include being consistent in risk formats (do not mix odds and percentages), using the same denominator across risk estimates, avoiding decimal points, including base rate information, and providing more explanation if the risk is less than 1%.

The communication of risk may be numerical, verbal, or visual. Use of multiple strategies may increase comprehension and retention of cancer genetic risk information.[2] Recently, use of visual risk communication strategies has increased (e.g., histograms, pie charts, and Venn diagrams). Visual depictions of risk may be very useful in avoiding problems with comprehension of numbers, but research that confirms this is lacking.[3,4] A study published in 2008 examined the use of two different visual aids to communicate breast cancer risk. Women at an increased risk of breast cancer were randomized to receive feedback via a bar graph alone or a bar graph plus a frequency diagram (i.e., highlighted human figures). Results indicate that overall, there were no differences in improved accuracy of risk perception between the two groups, but among those women who inaccurately perceived very high risk at baseline, the group receiving both visual aids showed greater improvement in accuracy.[5]

Risk Communication

The purpose of risk counseling is to provide individuals with accurate information about their risk, help them understand and interpret their risk, assist them as they use this information to make important health care decisions, and help them make the best possible adjustment to their situation. A systematic review of 28 studies that evaluated communication interventions showed that risk communication benefits users cognitively by increasing their knowledge and understanding of risk perception and does not negatively influence affect (anxiety, cancer-related worry, and depression). Risk communication does not appear to result in a change in use of screening practices and tests. Users received the most benefit from an approach utilizing risk communication along with genetic counseling.[6,7] Perceptions of risk are affected by the manner in which risk information is presented, difficulty understanding probability and heredity,[8,9] and other psychological processes on the part of individuals and providers.[10] Risk may be communicated in many ways (e.g., with numbers, words, or graphics; alone or in relation to other risks; as the probability of having an adverse event; in relative or absolute terms; and through combinations of these methods). The way in which risk information is communicated may affect the individual’s perception of the magnitude of that risk. In general, relative risk estimates (e.g., "You have a threefold increased risk of colorectal cancer") are perceived as less informative than absolute risk (e.g., "You have a 25% risk of colorectal cancer") [11] or risk information presented as a ratio (e.g., 1 in 4).[9] A strong preference for having BRCA1/BRCA2 pathogenic variant risk estimates expressed numerically is reported by women considering testing.[12] Individuals associate widely differing quantitative risks with qualitative descriptors of risk such as “rare” or “common.”[13] More research is needed on the best methods of communicating risk in order to help individuals develop an accurate understanding of their cancer risks.

Communication Strategies

Recent descriptive examination of the process of cancer genetic counseling has found that counseling sessions are predominantly focused on the biomedical teaching required to inform clients of their choices and to put genetic findings in perspective but that attention to psychosocial issues does not detract from teaching goals and may enhance satisfaction in clients undergoing counseling. For instance, one study of communication patterns in 167 pretest counseling sessions for BRCA1 found the sessions to have a predominantly biomedical and educational focus;[14] however, this approach was client focused, with the counselor and client contributing equally to the dialogue. These authors note that there was a marked diversity in counselor styles, both between counselors and within different sessions, for each counselor. The finding of a didactic style was corroborated by other researchers who examined observer-rated content checklists and videotape of 51 counseling sessions for breast cancer susceptibility.[15] Of note, genetic counselors seemed to rely on demographic information and breast cancer history to tailor genetic counseling sessions rather than client’s self-reported expectations or psychosocial factors.[16] Concurrent provision of psychosocial and scientific information may be important in reducing worry in the context of counseling about cancer genetics topics.[17] An increasing appreciation of language choices may contribute to enhanced understanding and reduced anxiety levels in the session; for example, it was noted that patients may appreciate synonymic choices for the word “mutation,” such as “altered gene”.[18] Some authors have published recommendations for cultural tailoring of educational materials for the African-American population, such as a large flip chart, including the use of simple language and pictures, culturally identifiable images (e.g., spiritual symbols and tribal patterns), bright colors, and humor.[19]

Studies have examined novel channels to communicate genetic cancer risk information, deliver psychosocial support, and standardize the genetic counseling process for individuals at increased risk of cancer.[20-27] Much of this literature has attempted to make the genetic counseling session more efficient or to limit the need for the counselor to address basic genetic principles in the session to free up time for the client’s personal and emotional concerns about his or her risk. For example, the receipt of genetic feedback for BRCA1/BRCA2 and mismatch repair gene testing by letter, rather than a face-to-face genetic counseling feedback session, has been investigated.[28] Other modalities include the development of patient assessments or checklists, CD-ROM programs, and interactive computer programs.

Patient assessments or checklists have been developed to facilitate coverage of important areas in the counseling session. One study assessed patients’ psychosocial needs before a hereditary cancer counseling session to determine the assessment’s effect on the session.[29] A total of 246 participants from two familial cancer clinics were randomly assigned to either an intervention arm in which the counselor received assessment results or a usual care control arm. Study results demonstrated that psychosocial concerns were discussed more frequently among intervention participants than among controls, without affecting session length. Moreover, cancer worry and psychological distress were significantly lower for intervention versus control participants 4 weeks after the counseling session.

A second study compared a feedback checklist completed by 197 women attending a high-risk breast clinic prior to the counseling session to convey prior genetic knowledge and misconceptions to aid the counselor in tailoring the session for that client.[22] The use of the feedback checklist led to gains in knowledge from the counseling session but did not reduce genetic counseling time, perhaps because the genetic counselor chose to spend time discussing topics such as psychosocial issues. Use of the checklist did decrease the time spent with the medical oncologist, however. The feedback checklist was compared with a CD-ROM that outlined basic genetic concepts and the benefits and limitations of testing and found that those viewing the CD-ROM spent less time with counselors and were less likely to choose to undergo genetic testing. The CD-ROM did not lead to increased knowledge of genetic concepts, as did use of the checklist.

A prospective study evaluated the effects of a CD-ROM decisional support aid for microsatellite instability (MSI) tumor testing in 239 colorectal cancer patients who met the revised Bethesda criteria but who did not meet the Amsterdam criteria.[30] The study also tested a theoretical model of factors influencing decisional conflict surrounding decisions to pursue MSI tumor testing. Within the study, half of the sample was randomly assigned to receive a brief description of MSI testing within the clinical encounter, and the other half was provided the CD-ROM decisional support aid in addition to the brief description. The CD-ROM and brief description intervention increased knowledge about MSI testing more than the brief description alone did. As a result, decisional conflict decreased because participants felt more prepared to make a decision about the test and had increased perceived benefits of MSI testing.

Other innovative strategies include educational materials and interactive computer technology. In one study, a 13-page color communication aid using a diverse format for conveying risk, including graphic representations and verbal descriptions, was developed.[23] The authors evaluated the influence of the communication aid in 27 women at high risk of a BRCA1/BRCA2 pathogenic variant and compared those who had read the aid to a comparison sample of 107 women who received standard genetic counseling. Improvements in genetic knowledge and accuracy of risk perception were documented in those who had read the aid, with no differences in anxiety or depression between groups. Personalized, interactive electronic materials have also been developed to aid in genetic education and counseling.[24,25] In one study, an interactive computer education program available prior to the genetic counseling session was compared with genetic counseling alone in women undergoing counseling for BRCA1/BRCA2 testing.[25] Use of the computer program prior to genetic counseling reduced face-time with the genetic counselor, particularly for those at lower risk of a BRCA1/BRCA2 pathogenic variant. Many of the counselors reported that their client’s use of the computer program allowed them to be more efficient and to reallocate time spent in the sessions to clients’ unique concerns.

Videoconferencing is an innovative strategy to facilitate genetic counseling sessions with clients who cannot travel to specialized clinic settings. In 37 individuals in the United Kingdom, real-time video conferencing was compared with face-to-face counseling sessions; both methods were found to improve knowledge and reduce anxiety levels.[26] Similarly, teleconferencing sessions, in which the client and genetic specialists were able to talk with each other in real time, were used in rural Maine communities [27] in the pediatric context to convey genetic information and findings for developmental delays and were found to be comparable to in-person consultations in terms of decision-making confidence and satisfaction with the consultations. An Australian study compared the experiences of 106 women who received hereditary breast and ovarian cancer genetic counseling via videoconferencing with the experiences of 89 women who received counseling face to face. Pre- and 1-month postcounseling assessments revealed no significant differences in knowledge gains, satisfaction, cancer-specific anxiety, generalized anxiety, depression, and perceived empathy of the genetic counselor.[31]

References

1. Baker DL, Schuette JL, Uhlmann WR, eds.: A Guide to Genetic Counseling. New York, NY: Wiley-Liss, 1998.
2. Lipkus IM: Numeric, verbal, and visual formats of conveying health risks: suggested best practices and future recommendations. Med Decis Making 27 (5): 696-713, 2007 Sep-Oct. [PUBMED Abstract]
3. Ancker JS, Senathirajah Y, Kukafka R, et al.: Design features of graphs in health risk communication: a systematic review. J Am Med Inform Assoc 13 (6): 608-18, 2006 Nov-Dec. [PUBMED Abstract]
4. Schapira MM, Nattinger AB, McHorney CA: Frequency or probability? A qualitative study of risk communication formats used in health care. Med Decis Making 21 (6): 459-67, 2001 Nov-Dec. [PUBMED Abstract]
5. Ghosh K, Crawford BJ, Pruthi S, et al.: Frequency format diagram and probability chart for breast cancer risk communication: a prospective, randomized trial. BMC Womens Health 8: 18, 2008. [PUBMED Abstract]
6. Edwards A, Gray J, Clarke A, et al.: Interventions to improve risk communication in clinical genetics: systematic review. Patient Educ Couns 71 (1): 4-25, 2008. [PUBMED Abstract]
7. Edwards A, Unigwe S, Elwyn G, et al.: Personalised risk communication for informed decision making about entering screening programs. Cochrane Database Syst Rev (1): CD001865, 2003. [PUBMED Abstract]
8. Marteau TM, van Duijn M, Ellis I: Effects of genetic screening on perceptions of health: a pilot study. J Med Genet 29 (1): 24-6, 1992. [PUBMED Abstract]
9. Hopwood P, Howell A, Lalloo F, et al.: Do women understand the odds? Risk perceptions and recall of risk information in women with a family history of breast cancer. Community Genet 6 (4): 214-23, 2003. [PUBMED Abstract]
10. Redelmeier DA, Koehler DJ, Liberman V, et al.: Probability judgement in medicine: discounting unspecified possibilities. Med Decis Making 15 (3): 227-30, 1995 Jul-Sep. [PUBMED Abstract]
11. Malenka DJ, Baron JA, Johansen S, et al.: The framing effect of relative and absolute risk. J Gen Intern Med 8 (10): 543-8, 1993. [PUBMED Abstract]
12. Winer E, Winer N, Bluman L, et al.: Attitudes and risk perceptions of women with breast cancer considering testing for BRCA1/2. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A1937, 537a, 1997.
13. Mazur DJ, Hickam DH: Patients' interpretations of probability terms. J Gen Intern Med 6 (3): 237-40, 1991 May-Jun. [PUBMED Abstract]
14. Ellington L, Baty BJ, McDonald J, et al.: Exploring genetic counseling communication patterns: the role of teaching and counseling approaches. J Genet Couns 15 (3): 179-89, 2006. [PUBMED Abstract]
15. Pieterse AH, van Dulmen S, van Dijk S, et al.: Risk communication in completed series of breast cancer genetic counseling visits. Genet Med 8 (11): 688-96, 2006. [PUBMED Abstract]
16. Lobb EA, Butow PN, Meiser B, et al.: Tailoring communication in consultations with women from high risk breast cancer families. Br J Cancer 87 (5): 502-8, 2002. [PUBMED Abstract]
17. Appleton S, Watson M, Rush R, et al.: A randomised controlled trial of a psychoeducational intervention for women at increased risk of breast cancer. Br J Cancer 90 (1): 41-7, 2004. [PUBMED Abstract]
18. Hodgson J, Hughes E, Lambert C: "SLANG"--Sensitive Language and the New Genetics--an exploratory study. J Genet Couns 14 (6): 415-21, 2005. [PUBMED Abstract]
19. Baty BJ, Kinney AY, Ellis SM: Developing culturally sensitive cancer genetics communication aids for African Americans. Am J Med Genet 118A (2): 146-55, 2003. [PUBMED Abstract]
20. Green MJ, Peterson SK, Baker MW, et al.: Effect of a computer-based decision aid on knowledge, perceptions, and intentions about genetic testing for breast cancer susceptibility: a randomized controlled trial. JAMA 292 (4): 442-52, 2004. [PUBMED Abstract]
21. Fransen M, Meertens R, Schrander-Stumpel C: Communication and risk presentation in genetic counseling. Development of a checklist. Patient Educ Couns 61 (1): 126-33, 2006. [PUBMED Abstract]
22. Wang C, Gonzalez R, Milliron KJ, et al.: Genetic counseling for BRCA1/2: a randomized controlled trial of two strategies to facilitate the education and counseling process. Am J Med Genet A 134 (1): 66-73, 2005. [PUBMED Abstract]
23. Lobb EA, Butow PN, Moore A, et al.: Development of a communication aid to facilitate risk communication in consultations with unaffected women from high risk breast cancer families: a pilot study. J Genet Couns 15 (5): 393-405, 2006. [PUBMED Abstract]
24. Mackay J, Schulz P, Rubinelli S, et al.: Online patient education and risk assessment: project OPERA from Cancerbackup. Putting inherited breast cancer risk information into context using argumentation theory. Patient Educ Couns 67 (3): 261-6, 2007. [PUBMED Abstract]
25. Green MJ, Peterson SK, Baker MW, et al.: Use of an educational computer program before genetic counseling for breast cancer susceptibility: effects on duration and content of counseling sessions. Genet Med 7 (4): 221-9, 2005. [PUBMED Abstract]
26. Coelho JJ, Arnold A, Nayler J, et al.: An assessment of the efficacy of cancer genetic counselling using real-time videoconferencing technology (telemedicine) compared to face-to-face consultations. Eur J Cancer 41 (15): 2257-61, 2005. [PUBMED Abstract]
27. Lea DH, Johnson JL, Ellingwood S, et al.: Telegenetics in Maine: Successful clinical and educational service delivery model developed from a 3-year pilot project. Genet Med 7 (1): 21-7, 2005. [PUBMED Abstract]
28. Voorwinden JS, Jaspers JP, ter Beest JG, et al.: The introduction of a choice to learn pre-symptomatic DNA test results for BRCA or Lynch syndrome either face-to-face or by letter. Clin Genet 81 (5): 421-9, 2012. [PUBMED Abstract]
29. Eijzenga W, Aaronson NK, Hahn DE, et al.: Effect of routine assessment of specific psychosocial problems on personalized communication, counselors’ awareness, and distress levels in cancer genetic counseling practice: a randomized controlled trial. J Clin Oncol 32 (27): 2998-3004, 2014. [PUBMED Abstract]
30. Hall MJ, Manne SL, Winkel G, et al.: Effects of a decision support intervention on decisional conflict associated with microsatellite instability testing. Cancer Epidemiol Biomarkers Prev 20 (2): 249-54, 2011. [PUBMED Abstract]
31. Zilliacus EM, Meiser B, Lobb EA, et al.: Are videoconferenced consultations as effective as face-to-face consultations for hereditary breast and ovarian cancer genetic counseling? Genet Med 13 (11): 933-41, 2011. [PUBMED Abstract]

Ethical, Legal, and Social Implications

In This Section

• Bioethical Issues in Cancer Genetic Testing
  • Beneficence
  • Nonmaleficence
  • Autonomy
  • Justice
• Privacy and Confidentiality: Disclosure of Patient’s Genetic Information
  • Disclosure in research
  • “Duty to warn”: Legal proceedings, federal/state legislation, and recommendations of professional organizations
• Employment and Insurance Discrimination
  • Legal proceedings, federal/state legislation, and recommendations of professional organizations
  • Professional guidelines and other resources

Having an understanding of the ethical, legal, and social implications (ELSI) regarding cancer genetic testing may influence the clinician’s response to the complex questions and issues that may arise during the process of risk assessment and counseling. This section discusses biomedical ethics codes, legal and social issues relevant to privacy, and fair use in the interpretation of genetic information. In order to integrate the different perspectives of bioethics, law, and psychosocial influences, case scenarios are offered to illustrate dilemmas encountered in the clinical setting. (Refer to the Determining the Test to Be Used section of this summary for more information about the regulation of genetic tests.)

Bioethical Issues in Cancer Genetic Testing

Bioethical tenets can guide health care providers in dealing with the complex issues surrounding predictive testing for hereditary cancer. The tenets of beneficence, nonmaleficence, autonomy, and justice are part of a framework needed to balance the complex and potentially conflicting factors surrounding a clinician’s role in respecting privacy, confidentiality and fair use of genetic information obtained from cancer genetic testing.

Beneficence

The concept of beneficence dictates that the primary goal of medical care is to provide benefit through appropriate health care.[1] In the field of oncology, this translates into using early detection and effective treatment protocols to improve outcomes. Providing beneficent care may go beyond medical outcomes of treatment to encompass the patient’s life circumstances, expectations, and values.[1] Consideration of the patient’s psychological and emotional ability to handle the testing and results disclosure process can help avoid doing harm.[2] (Refer to the Psychological Impact of Genetic Testing/Test Results on the Individual section of this summary for more information.)

Nonmaleficence

Nonmaleficence is the bioethical code that directs health care providers to do no harm, inclusive of physical and emotional harm, and acknowledges that medical care involves risks and benefits.[1] Particular to the field of oncology, adherence to this construct includes taking measures to minimize the adverse effects of cancer prevention, treatment, and control. This may encompass taking precautionary measures to prevent inadvertent disclosure of sensitive information.[2]

Autonomy

Autonomous decision making respects individual preferences by incorporating informed consent and education.[1] Individuals have the right to be informed about the risks and benefits of genetic testing and to freely choose or decline testing for themselves. Additionally, it is beneficial to consider the sociocultural context and family dynamics to ensure medical decision making takes places without coercion or interference.[1]

Justice

Justice refers to the equitable distribution of the benefits and risks of health care.[1] A goal in oncology is ensuring access to cancer genetic services. The availability of predictive genetic testing should not be dependent on ethnic background, geographical location, or ability to pay. Genetic discrimination should not be a result of predictive testing.[2] Equitable distribution balances individual rights with responsibilities of community membership.[1]

Privacy and Confidentiality: Disclosure of Patient’s Genetic Information

A strong provider-patient relationship is founded on respect for the patient’s privacy and confidentiality; therefore, protecting the patient’s personal information from third parties is key to building trust.[2,3] Predictive testing for cancer susceptibility presents a challenge because of the hereditary nature of the diseases being tested and the implications of genetic risk for family members. Physicians are faced with a duty to warn or to act to prevent foreseeable harm.[4] One practical suggestion for facilitating family-based communication is providing patients with education and information materials to facilitate disease susceptibility discussions with family members.[1] The next section discusses the legal, legislative, and ethical basis for balancing patient confidentiality with duty to warn.

Disclosure in research

Privacy and confidentiality also applies to research, such as population screening for genetic diseases. The U.S. Department of Health and Human Services authorizes the use of Certificates of Confidentiality to researchers.[5] This certificate, issued by the National Institutes of Health, protects the researcher from having to reveal the identity of any research subject “in any Federal, State, or local civil, criminal, administrative, legislative, or other proceedings.” The protections offered by the certificate of confidentiality are limited to personally identifiable information collected beginning on the date of issuance and ending on the expiration date, which matches the date of study completion. The NIH Office of Extramural Research policy and guidance on Certificates of Confidentiality notes that any personally identifiable information collected during that time interval is protected in perpetuity. In regard to family-based recruitment strategies, the Cancer Genetics Network Bioethics Committee assembled a group of experts to develop recommendations for researchers to use in approaching family members.[6] Due to the wide spectrum of research strategies, there are different levels of concern. Essential to family-based recruitment strategies is informing potential research participants how their personal information was obtained by the researcher, why the researcher is approaching them, what the researcher knows about them, and for what purpose the information will be used, whether or not they decide to participate.[6]

“Duty to warn”: Legal proceedings, federal/state legislation, and recommendations of professional organizations

“Duty to warn” requires balancing the bioethical constructs of beneficence and autonomy with other factors such as case proceedings, legislation, and professional societies’ recommendations. As of September 2008, the National Council of State Legislatures lists the statesExit Disclaimer that have legislation requiring consent to disclose genetic information. The definition of "genetic information" can vary depending on the legal case and the language used in state and federal legislation, and generally includes genetic testing and family history information; however, the definition generally does not apply to current diagnoses. Genetic diagnosis can be done through direct genetic tests for disorders linked to a specific gene and indirect genetic tests for disorders in which the specific genes are not known or there are multiple different genes involved (genetic heterogeneity).[7] There are four state case laws that apply to duty to warn.[8] Two cases deal directly with testing for hereditary cancer predisposition syndromes; one case deals with a psychotherapist's duty to warn a relative of imminent threat, and another with genetic testing as a tool for reproductive decisions. Table 3 summarizes the cases.

Table 3. State Case Laws That Apply to Duty to Warn

State Case Law	Description	Summary
Tarasoff versus Regents of the University of California [9,10]	Establishes moral duty to warn family members of risks unknown to them	In 1976, the California court judged that breach of confidentiality would have been justified in order to warn of a foreseeable and serious harm to an identifiable individual.
	Distinct from genetic risk since the pathogenic variant is already present (or absent) in family members
Pate versus Threlkel [8,11,12]	Duty to warn family members of hereditary risk of cancer is satisfied by telling the patient to tell his or her family	In 1995, the Florida court judged that a physician had a duty to warn the patient that her children were at risk of developing thyroid cancer because the disease could have been detected and cured at an earlier stage.
Safer versus Estate of Pack [8,13]	Physician must take reasonable steps to warn family members of hereditary risk disease	In 1996, a New Jersey appellate court defined a physician’s duty to warn immediate family members of risk of colon cancer; however, the court ruled in favor of the doctor because the patient had undergone rectal screening as a child, which indicated that she had been warned of the risk.
Molloy versus Meier [8,14]	Physician’s duty regarding genetic testing and diagnosis of foreseeable disease risk extends beyond the patient to biological parents	In 2004, a Minnesota Supreme Court held that the physician failed to breach confidentiality to warn of hereditary disease risk because he did not inform parents of the diagnosis of fragile X syndrome in their first child. The parents state that this information would have influenced their reproductive decisions.

At the federal level, there are strict nondisclosure policies governing private health information.[8] The Standards for Privacy of Individually Identifiable Health Information (Privacy Rule), which summarizes the Health Insurance Portability and Accountability Act (HIPAA) of 1996, finds it permissible to disclose health information without consent when the public interest is at risk;[15,16] therefore, under certain conditions, there are exceptions to the nondisclosure policy include the following:

1. There is serious or imminent threat to the health or safety of a person or the public.
2. The threat constitutes an imminent, serious threat to an identifiable third party.
3. The physician has the capacity to avert significant harm.

Professional societies and government advisory agencies have published their different positions and recommendations on communication between a physician and a patient's relatives in regard to disclosure of genetic disease.[4,8,17]

The Council on Ethical and Judicial Affairs of the American Medical AssociationExit Disclaimer (AMA) and the American Society of Clinical Oncology (ASCO) [18,19] encourage discussing the importance of patients sharing genetic information with family members.[4] Specifically, the Council on Ethical and Judicial Affairs of the American Medical AssociationExit Disclaimer states that “Physicians …should identify circumstances under which they would expect patients to notify biological relatives of the availability of information related to risk of disease…(and) physicians should make themselves available to assist patients in communicating with relatives to discuss opportunities for counseling and testing, as appropriate.” ASCO’s position is that providers “should remind patients of the importance of communicating test results to family members… ASCO believes that the cancer care provider’s obligations (if any) to at-risk relatives are best fulfilled by communication of familial risk to the person undergoing testing, emphasizing the importance of sharing this information with family members so that they may also benefit.”[18] These organizations recommend that family members disclose genetic information.

The National Society of Genetic Counselors [20] and the International Society of Nurses in Genetics [21] support the release of any genetic information upon request to third parties including relatives but only with the patient's consent.[4] One of the tenets of genetic counseling is to maintain information received from clients as confidential, unless released by the client or consent for disclosure is provided as required by law.[4,20]

Similar to the Privacy Rule, the U.S. Bioethics Commission,[22] American Society of Human Genetics,[23] and National Human Genome Research Institute (NHGRI) recommend the following guidelines to identify exceptional circumstances under which it is ethically acceptable to breach confidentiality.[4,8]

1. There is a high likelihood of harm if the relative is not warned.[4,22,23]
2. The patient, despite encouragement, refuses to inform family members.[4,22,23]
3. The relative is identifiable.[23]
4. The harm of nondisclosure is greater than the harm of disclosure.[23]
5. Current medical technology renders the disease preventable, treatable, or manageable.[23]
6. Only the information necessary to prevent harm is released.[4,24]
7. There is no other reasonable way to avert harm.[4]

At an international level, the World Health Organization and World Medical Association have similar guidelines.[4] Additionally, Australia, Canada, Germany, Japan, the Netherlands, and the United Kingdom have guidelines supporting the disclosure of genetic information to relatives under similar exceptional circumstances.[4]

Employment and Insurance Discrimination

Genetic information obtained from genetic susceptibility tests may have medical, economic, and psychosocial implications for the individual tested and his or her family members. The potential for employment and insurance discrimination is a common concern for individuals considering genetic testing.[25,26] However, there is limited documentation of the occurrence of employment and insurance discrimination on the basis of hereditary cancer genetic testing results.

Public awareness of the federal Genetic Information Nondiscrimination Act (GINA) and its protections is limited. In a multistate survey conducted in 2010, more than 80% of respondents indicated that they were unaware of the law.[27] In a 2014 survey of 1,479 U.S. adults, 79% indicated that they were unaware of the law.[28] Of those who were aware of GINA, 44% knew that it protected against health insurance and 33% knew it protected against employment discrimination; 23% incorrectly believed the law protected against life, disability, and long-term insurance discrimination. After reading a description of GINA, 30% of respondents indicated that they were actually more concerned about discrimination [note: The denominator for the latter finding is uncertain]. Although genetic testing has increased since the passage of the law, relatively few cases of discrimination in which GINA’s authority can be tested have been reported.[28]

(Refer to the Informed Consent subsection of this summary for more information.)

Legal proceedings, federal/state legislation, and recommendations of professional organizations

A legal case example at the federal district court level involves the Burlington Northern Santa Fe Railroad. The U.S. Equal Employment and Opportunities Commission requested that Burlington Northern Santa Fe Railroad not be allowed to use medical information obtained from genetic tests for employment decisions.[24]

In the last 15 years, state and federal legislation statutes have been developed to prevent the use of genetic information for employment practices, such as hiring, promotion, and salary decisions; and insurance policies, including life and health coverage, by employers, schools, government agencies, and insurers.[12] According to Executive Order 13145, federal departments and agencies are prohibited from discriminating against employees on the basis of genetic test results or information about a request for genetic testing services.[24] Employers and insurers are prohibited from intentionally lowering policy rates by using practices such as screening for individuals who are at risk of becoming ill or dying due to genetic disease susceptibility, such as cancer.[24] Federal laws, including GINA, do not cover employer-provided life and disability; however, some states do have legislation addressing the use of genetic information for life and disability policies. The National Conference of State Legislatures (NCSL) [29,30] summarized current health legislation of the U.S. Congress. Examples of relevant legislation regarding genetic information include, GINA, HIPAA, Americans with Disabilities Act (ADA), and Employee Retirement Income Security Act (ERISA).

Table 4. Comparison of Federal Legislation Addressing Genetic Coverage, Limitations, and Protectionsa

Law	Coverage	Limitations	Protect All Americans
aAdapted from Leib et al.[31]
Civil Rights Act of 1964	Employment only	Does not apply to health insurance	Yes
	Applies in instances of discrimination based on genetic information if associated with race or ethnic groups	Strong association with a racial or ethnic group for hereditary cancers is rare
Americans with Disabilities Act of 1990	Disabilities associated with manifesting genetic information	Does not apply to health insurance	Yes
Health Insurance Portability and Accountability Act of 1996	Group health insurance plans	Does not stop insurers from requiring genetic tests	Yes
		Genetic information is not defined
	Forbids excluding an individual in a group health plan due to genetic information	Genetic information can be used for plan underwriting
	Forbids premium increases for different group plan members	Disclosure of genetic information is not restricted
	Preexisting conditions can not include predictive genetic information	Does not apply to individual health plans, unless covered by the portability provision
Executive Order 13145 of 2000	Forbids Federal employee workplace genetic discrimination	Does not apply to health insurance	No; excludes members of the United States military and anyone who is NOT a federal employee
		Only applies to Federal employees
Genetic Information Nondiscrimination Act of 2008 (GINA) (Enacted in 2009)	Forbids genetic discrimination in the workplace and in health insurance	Civil suit is restricted to only those who have had all administrative remedies exhausted	No; excludes members of the United States military, veterans obtaining health care through the Veteran’s Administration, and the Indian Health Service
	Genetic information broadly defined
	Specific to group and individual insurance plans
	Forbids use of genetic information in underwriting
	Forbids requiring genetic testing by employers and insurers	Does not cover life, disability, and long-term care insurance

Genetic Information Nondiscrimination Act 2008

GINA 2008 protects the provision of health insurance and employment against discrimination based on genetic information as follows:

• Prohibits access to individuals’ personal genetic information by insurance companies and by employers.[32]
• Prohibits insurance companies from requesting that applicants for group or individual health coverage plans be subjected to genetic testing or screening and prohibits them from discriminating against health plan applicants based on individual genetic information.[32]
• Prohibits employers from using genetic information to refuse employment, and prohibits them from collecting employees’ personal genetic information without their explicit consent.[32]
• Prohibits employment agencies from failing or refusing to refer a candidate on the basis of genetic information.[33]
• Prohibits labor organizations from refusing membership based on a member's genetic make-up.[33]
• Does not mandate coverage for medical tests or treatments.[34]
• Does not prohibit medical underwriting based on current health status.[34]
• Does not limit a treating health provider, including those employed by or affiliated with health plans, from requesting or notifying individuals about genetic tests.[35]
• Does not prohibit occupational testing for toxic monitoring programs, employer-sponsored wellness programs, administration of federal and state family and medical leave laws, and certain cases of inadvertent acquisition of genetic information.[36]

GINA amends and/or extends coverage of HIPAA, ADA, and ERISA by including genetic information under medical privacy and confidentiality legislation and employment and insurance determinations.[29] Additionally, with the passage of GINA, researchers and clinicians can encourage participation in clinical trials and appropriate genetic testing knowing that there are federal protections against discrimination based on the results of genetic testing. GINA established the minimum protection level that must be met in all states. However, for states with more robust legislation in place, GINA does not weaken existing protections provided by state law.

However, GINA has several limitations.

1. GINA does not apply to members of the United States military, to veterans obtaining health care through the Veteran’s Administration, or to the Indian Health Service because the laws amended by GINA do not apply to these groups and programs.
2. The legislation does not apply to life insurance, long-term care insurance, or disability insurance. Even though GINA does not provide protection for employer-provided disability and life insurance, some states do encompass these arenas in addition to employment, genetic privacy, health insurance, health insurance enforcement, life, disability, and long-term care. NHGRI's Genome Statute and Legislation Database provides a searchable listing of state statutes and bills related to the following topics: direct-to-consumer genetic testing, employment and insurance nondiscrimination, health insurance coverage, privacy, research, and the use of residual newborn screening specimens.
3. GINA’s employment provisions generally do not apply to employers with fewer than 15 employees.[34]

A study conducted between 2009 and 2010 via a survey posted on the Facing Our Risk of Cancer Empowered (FORCE) website provides insight into consumers' perspectives regarding insurance discrimination based on genetic test results after the passage of GINA. Of the 1,669 participants (69% of whom previously received genetic testing), 53% indicated that they had heard about insurance discrimination based on genetic test results. More than half the sample (54%) reported that they had not heard about GINA before the survey. After being provided with a brief description of GINA as part of the survey process, 60% (n = 886) reported a change in their feelings about genetic testing, with the majority (573 of 886 participants) indicating less concern about health insurance discrimination. Finally, when asked whom they would contact regarding questions about GINA, 38% indicated their health care provider.[37]

Exception to protections against employment and insurance discrimination: Active duty military personnel

GINA and other state and federal protections do not extend to genetic testing of active duty military personnel or genetic information obtained from active duty military personnel.[38] In the military, genetic testing provides medical information that is to be used to protect military personnel from harmful duty or other exposures that could stimulate or aggravate a health problem. For example, use of certain antimalaria medication in individuals with glucose 6-phosphate dehydrogenase deficiency can result in red blood cell rupture. Therefore, some genetic information is critical for maintaining the health and safety of military personnel, given the possible stressful occupational environments they face. In addition, all military personnel provide a DNA sample to be maintained in a repository that can be used for identification purposes.[39]

Results of genetic tests for disease predisposition could influence military eligibility for new enlistments, and for current military personnel, genetic test results could influence worldwide eligibility, assignments, and promotions. For example, a young woman found to carry a BRCA pathogenic variant may not be considered eligible for deployment for 12-15 months because access to recommended health care may not be easily accessible, such as breast MRI, a recommended screening modality for carriers of BRCA pathogenic variants. Active duty military personnel with less than eight years of active duty service are especially vulnerable in the event they become disabled and must go before the medical board to establish benefit eligibility.

In 2006, Department of Defense Instruction Number 1332.38 (DODINST 1332.38) redefined preexisting condition as a result of two cases brought by service members who each had a hereditary condition that presented later in their military careers. The disability instructions state that any injury or disease discovered after a service member enters active duty—with the exception of congenital and hereditary conditions—is presumed to have been incurred in the line of duty. Any hereditary and/or genetic disease shall be presumed to have been incurred prior to entry into active duty. However, DODINST 1332.38 further states that any aggravation of that disease, incurred in the line of duty, beyond that determined to be due to natural progression, shall be deemed service aggravated. As a result of these two cases, the 8-year active duty service limit was established. This means that after 8 or more years of military service, the natural progression of a genetic condition would be deemed aggravated by military service. Therefore, until late 2008, the presence of a congenital or hereditary condition would not be considered a preexisting condition in disability decision making for those with 8 or more years of service.

In October 2008, in response to the National Defense Authorization Act of 2008 (NDAA) Title XVI: “Wounded Warrior Matters,” a policy memorandum was issued providing supplemental and clarifying guidance on implementing disability-related provisions, including new language related to hereditary or genetic diseases. The policy memorandum states, “Any hereditary or genetic disease shall be evaluated to determine whether clear and unmistakable evidence demonstrates that the disability existed before the Service member’s entrance on active duty and was not aggravated by military service. However, even if the conclusion is that the disability was incurred prior to entry on active duty, any aggravation of that disease, incurred while the member is entitled to basic pay, beyond that determined to be due to natural progression shall be determined to be service aggravated.” The interpretation of this policy is uncertain at this time.[39]

Case scenarios involving ELSI issues in cancer genetic testing

There are multiple psychosocial, ethical, and legal issues to consider in cancer genetic testing. Genetic tests for germline pathogenic variants have social and family implications. In addition to prevention and surveillance options, genetic testing should be offered in conjunction with genetic education and counseling.[18,19] A comprehensive strategy for dealing with ethical dilemmas can incorporate a shared approach to decision making, including open discussion, planning, and involvement of the family.[5] To integrate the different perspectives of bioethics, law, and psychosocial influences, the following scenarios can help health care providers become familiar with commonly encountered dilemmas; it is imperative, however, that the clinician evaluate each patient and his or her situation on a case-by-case basis. These case scenarios were adopted from “Counseling about Cancer: Strategies for Genetic Counseling;” the in-depth case examples are extensively discussed in the original text.[2]

Duty to warn versus privacy

A patient with known family history of breast cancer is interested in testing for BRCA1 and BRCA2 pathogenic variant. In reviewing her family history, the health care provider realizes that the patient is not aware of an additional rare but hereditary cancer pathogenic variant in a second-degree relative, which the health center tested and confirmed in the past. After talking with her family, the patient is unable to confirm the details of the second hereditary cancer pathogenic variant and again expresses interest in BRCA1/BRCA2 testing. Does the health care provider have a “duty to warn” the patient of the unknown cancer susceptibility gene in the family, at the risk of disclosing private patient information? The following issues are important to consider in resolving this case.

1. Preserving the confidentiality of the relative and informing the patient of her cancer risk are both important goals. In general, the health care professional has a “Duty to warn” when there is a high likelihood of harm if not warned, the person at risk is identifiable, the harm of nondisclosure is greater than disclosure, and only the information necessary to prevent harm is released. (Refer to the Privacy and Confidentiality: Disclosure of Patient’s Genetic Information section of this summary for more information.)
2. It is possible that the benefit outweighs the harm of informing the patient of the second cancer syndrome because the monitoring and management of the rare cancer are different from guidelines for the general population. Additionally both parties are identifiable. An option is to contact the relative for permission to disclose the genetic test result to the patient in question.
3. If it is not possible to obtain permission to disclose, it is possible to inform the patient that she meets clinical criteria for the hereditary cancer syndrome without releasing specific information about the genetic test results of the relative.

Patient’s right to know versus family member’s autonomy

A patient with a family history of a hereditary cancer is interested in predictive genetic testing and convinces an affected family member, who initially expresses unwillingness, to be tested in order to establish the familial pathogenic variant. In this scenario, the surviving family member admits to feeling pressured into consenting for genetic testing. Both the patient and the affected family member are patients. What takes precedence—the patient’s right to know or the family member’s autonomy? The following issues are important to consider in resolving this case.

1. Explore, with the patient, alternatives to testing that do not involve the participation of the unwilling family member, such as testing stored tissue of a deceased relative. (Refer to the Value of testing an affected family member first section of this summary for more information).
2. If the patient does not want to consider other options and the family member has agreed to be tested without coercion or interference, inform the family member of the implications of the test results, including risks and benefits, and assess her emotional well-being prior to testing.[20] (Refer to the Informed Consent section of this summary for more information.)

Right to know versus right not to know

A hereditary cancer syndrome has been identified in a family. Within that family, an adult child wants a cancer susceptibility test that her parent declined, and one identical twin wants testing but the other does not. Even though the uninterested parties have declined testing and do not want to know the results, it is possible that testing one relative can disclose results for the other family members. Do the rights of the family members interested in predictive testing take precedence over the rights of the relatives who do not want to know? The following issues are important to consider in resolving this case.

1. In hereditary cancer syndromes, an individual’s right to know takes precedence over an individual’s right not to know especially if there are early detection and prevention strategies to reduce the likelihood of morbidity and mortality.
2. Since the family has a documented pathogenic variant, standard of care recommendations include guidelines for screening and monitoring. In the event that testing is not done, it is important to take “reasonable steps” to guarantee immediate family members are warned of the hereditary cancer risk. (Refer to the Privacy and Confidentiality: Disclosure of Patient’s Genetic Information section of this summary for more information.)
3. Pretest and posttest discussions can include the possibility of medical, psychological, and social impact on family members and strategies on how to lessen any negative impact. The patient should honor the wishes of relatives who request not to know and attempt to keep the results secret.[20]

Beneficence versus paternalism

A psychological assessment of a patient interested in predictive testing for an autosomal dominant cancer reveals a history of depression and suicidal attempts. The health care provider is considering denying or deferring testing because of concerns for the patient’s emotional well-being even though the patient refuses a referral to a psychologist because he reports feeling emotionally stable. Is deferring or denying predictive genetic testing a beneficent gesture or an act of paternalism? The following issues are important to consider in resolving this case.

1. Despite the patient’s refusal to speak with a psychologist, the health care provider can discuss the details of the case with a mental health professional to determine suicidal risk. (Refer to the Psychological Impact of Genetic Information/Test Results on the Individual section of this summary for more information.)
2. If there is risk of psychosocial disturbances because of test results, it is possible to defer testing. Conditions under which testing can resume are explained to the patient. For example, the NSGC Code of Ethics recommends that clients be referred to other qualified professionals when the patient requires additional services.[20]
3. Denying a test does not seem justifiable under any circumstances because it implies that the client will never be able to undergo testing.

Professional guidelines and other resources

(Refer to the Genetic Resources section of the PDQ Cancer Genetics Overview summary for more information about the ELSI of genetic testing and counseling.)

References

1. Burke W, Press N: Genetics as a tool to improve cancer outcomes: ethics and policy. Nat Rev Cancer 6 (6): 476-82, 2006. [PUBMED Abstract]
2. Schneider K: The ethical issues. In: Schneider KA: Counseling About Cancer: Strategies for Genetic Counseling. 2nd ed. New York, NY: Wiley-Liss, 2002, pp 291-312.
3. Offit K: Clinical Cancer Genetics: Risk Counseling and Management. New York, NY: John Wiley and Sons, 1998.
4. Godard B, Hurlimann T, Letendre M, et al.: Guidelines for disclosing genetic information to family members: from development to use. Fam Cancer 5 (1): 103-16, 2006. [PUBMED Abstract]
5. Offit K: Psychological, ethical, and legal issues in cancer risk counseling. In: Offit K: Clinical Cancer Genetics: Risk Counseling and Management. New York, NY: John Wiley and Sons, 1998, pp 287-315.
6. Beskow LM, Botkin JR, Daly M, et al.: Ethical issues in identifying and recruiting participants for familial genetic research. Am J Med Genet A 130A (4): 424-31, 2004. [PUBMED Abstract]
7. Tantravahi U, Wheeler P: Molecular genetic testing for prenatal diagnosis. Clin Lab Med 23 (2): 481-502, 2003. [PUBMED Abstract]
8. Offit K, Groeger E, Turner S, et al.: The "duty to warn" a patient's family members about hereditary disease risks. JAMA 292 (12): 1469-73, 2004. [PUBMED Abstract]
9. California requires psychiatrists to warn about dangerous patients - Tarasoff v. Regents of University of California, 17 Cal. 3d 425, 551 P.2d 334, 131 Cal. Rptr. 14 (Cal. 1976). 1976. Also available onlineExit Disclaimer. Last accessed June 24, 2019.
10. Harris M, Winship I, Spriggs M: Controversies and ethical issues in cancer-genetics clinics. Lancet Oncol 6 (5): 301-10, 2005. [PUBMED Abstract]
11. Pate v. Threlkel, 661 So. 2d 278 (Florida 1995). 1995. Also available onlineExit Disclaimer. Last accessed June 24, 2019.
12. Sankar P: Genetic privacy. Annu Rev Med 54: 393-407, 2003. [PUBMED Abstract]
13. Safer v. Estate of Pack, 677 A2d 1188 (NJ App), appeal denied, 683 A2d 1163 (NJ 1996). 1996. Also available onlineExit Disclaimer. Last accessed June 24, 2019.
14. Molloy v. Meier, Nos. C9-02-1821, C2-02-1837 (Minn 2004). 2004. Also available onlineExit Disclaimer. Last accessed June 24, 2019.
15. Health Insurance Portability and Accountability Act of 1996, Public Law 104-191, 104th Congress. Washington, DC: 1996. Also available online. Last accessed June 24, 2019.
16. US Department of Health and Human Services: OCR Privacy Brief: Summary of the HIPAA Privacy Rule. Washington, DC: US Department of Health and Human Services, 2002. Also available online. Last accessed June 24, 2019.
17. Gordijn B: Genetic diagnosis, confidentiality and counseling: an ethics committee's potential deliberations about the do's and don'ts. HEC Forum 19 (4): 303-12, 2007. [PUBMED Abstract]
18. Robson ME, Storm CD, Weitzel J, et al.: American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol 28 (5): 893-901, 2010. [PUBMED Abstract]
19. Robson ME, Bradbury AR, Arun B, et al.: American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility. J Clin Oncol 33 (31): 3660-7, 2015. [PUBMED Abstract]
20. National Society of Genetic Counselors: National Society of Genetic Counselors Code of Ethics. Chicago, Il: National Society of Genetic Counselors, 2006. Also available onlineExit Disclaimer. Last accessed June 24, 2019.
21. International Society of Nurses in Genetics: Position Statements: Privacy and Confidentiality of Genetic Information: The Role of the Nurse. Pittsburgh, Pa: International Society of Nurses in Genetics, 2010. Also available onlineExit Disclaimer. Last accessed June 24, 2019.
22. US President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research: Screening and Counseling for Genetic Conditions: The Ethical, Social, and Legal Implications of Genetic Screening, Counseling, and Education Programs. Washington, DC: Government Printing Office, 1983. Also available onlineExit Disclaimer. Last accessed June 24, 2019.
23. ASHG statement. Professional disclosure of familial genetic information. The American Society of Human Genetics Social Issues Subcommittee on Familial Disclosure. Am J Hum Genet 62 (2): 474-83, 1998. [PUBMED Abstract]
24. Lowrey KM: Legal and ethical issues in cancer genetics nursing. Semin Oncol Nurs 20 (3): 203-8, 2004. [PUBMED Abstract]
25. Wauters A, Van Hoyweghen I: Global trends on fears and concerns of genetic discrimination: a systematic literature review. J Hum Genet 61 (4): 275-82, 2016. [PUBMED Abstract]
26. Prince AE, Roche MI: Genetic information, non-discrimination, and privacy protections in genetic counseling practice. J Genet Couns 23 (6): 891-902, 2014. [PUBMED Abstract]
27. Parkman AA, Foland J, Anderson B, et al.: Public awareness of genetic nondiscrimination laws in four states and perceived importance of life insurance protections. J Genet Couns 24 (3): 512-21, 2015. [PUBMED Abstract]
28. Green RC, Lautenbach D, McGuire AL: GINA, genetic discrimination, and genomic medicine. N Engl J Med 372 (5): 397-9, 2015. [PUBMED Abstract]
29. National Conference of State Legislatures: Summary: Selected Health Legislation 110th Congress. Washington, DC: National Conference of State Legislatures, 2008. Also available onlineExit Disclaimer. Last accessed June 24, 2019.
30. National Human Genome Research Institute: National Human Genome Research Institute Genome Statute and Legislation Database. Bethesda, Md: National Humokayan Genome Research Institute, 2008. Also available online. Last accessed June 24, 2019.
31. Leib JR, Hoodfar E, Haidle JL, et al.: The new genetic privacy law: how GINA will affect patients seeking counseling and testing for inherited cancer risk. Community Oncology 5 (6): 351-4, 2008.
32. American Society of Human Genetics: Genetic Scientists Applaud U.S. Senate Passage of the Genetic Information Nondiscrimination Act: American Society of Human Genetics Supports Important New Legislation [Press Release - April 25, 2008]. Bethesda, Md: American Society of Human Genetics, 2008. Also available onlineExit Disclaimer. Last accessed June 24, 2019.
33. Asmonga D: Getting to know GINA. An overview of the Genetic Information Nondiscrimination Act. J AHIMA 79 (7): 18, 20, 22, 2008. [PUBMED Abstract]
34. National Human Genome Research Institute: "GINA": The Genetic Information Nondiscrimination Act of 2008: Information for Researchers and Health Care Professionals. Bethesda, MD: National Human Genome Research Institute, 2009. Available online. Last accessed June 24, 2019.
35. United States Department of Labor: Frequently Asked Questions Regarding the Genetic Information Nondiscrimination Act. Washington, DC: United States Department of Labor, 2010. Available online. Last accessed June 24, 2019.
36. U.S. Equal Employment Opportunity Commission: The Genetic Information Nondiscrimination Act of 2008. Washington, DC: U.S. Equal Employment Opportunity Commission, 2008. Available online. Last accessed June 24, 2019.
37. Allain DC, Friedman S, Senter L: Consumer awareness and attitudes about insurance discrimination post enactment of the Genetic Information Nondiscrimination Act. Fam Cancer 11 (4): 637-44, 2012. [PUBMED Abstract]
38. Hudson KL, Holohan MK, Collins FS: Keeping pace with the times--the Genetic Information Nondiscrimination Act of 2008. N Engl J Med 358 (25): 2661-3, 2008. [PUBMED Abstract]
39. Baruch S, Hudson K: Civilian and military genetics: nondiscrimination policy in a post-GINA world. Am J Hum Genet 83 (4): 435-44, 2008. [PUBMED Abstract]

Changes to This Summary (11/08/2019)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Introduction

Updated National Comprehensive Cancer Network (NCCN): Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal as reference 13.

Identification of Candidates for Referral to Genetic Counseling

Updated NCCN: Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal as reference 3.

Cancer Risk Assessment and Counseling

Updated NCCN: Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal as reference 13.

Components of the Risk Assessment Process

Updated NCCN: Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal as reference 34.

The Option of Genetic Testing

Added text to state that the American Society of Clinical Oncology's (ASCO) 2010 and 2015 policy statements addressed testing for low- to moderate-penetrance genes and direct-to-consumer testing.

Added text to state that in 2015, ASCO updated its policy to address the challenges of new technologies in cancer genetics, including multigene (panel) testing for cancer genetic susceptibility, as well as incidental germline findings from somatic mutation profiling. ASCO's statement expressed support for communicating medically relevant germline findings discovered in the context of somatic mutation profiling.

The Genetic testing and assisted reproductive technology subsection was extensively revised.

Added text to state that in light of the heterogeneity in presentation and potential overlap in phenotypes among the various hereditary cancer syndromes, the selection of the appropriate genetic test for a given individual requires knowledge of genetic syndromes, molecular diagnostic methods used for identifying pathogenic variants, correlation between clinical and molecular findings, and access to information about rapidly changing testing options.

Added text to state that in selected reports from 2014 to 2018, variants of uncertain significance (VUS) rates were higher in non-white individuals, likely because of the limited availability of test result data needed for accurate determination of risk (cited Caswell-Jin et al. as reference 38).

Added text to state that in October 2014, the U.S. Food and Drug Administration (FDA) posted the notification regarding its plans to develop draft guidance on the regulation of laboratory-developed tests (cited FDA as reference 53). Draft guidance documents outlining the framework for regulatory oversight for the industry and clinical laboratories were published later in 2014 for public review and comment. Given the potential of such regulatory action to affect the wide spectrum of genetic tests currently in clinical practice, proposed draft guidelines have been discussed and reviewed by a number of professional associations. The issue of FDA oversight of laboratory-developed tests remains under consideration.

Revised text to state that the core elements of informed consent include a discussion of possible outcomes of testing (e.g., true positive, true negative, VUS, inconclusive, false positive, false negative).

This summary is written and maintained by the PDQ Cancer Genetics Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about cancer genetics risk assessment and counseling. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Cancer Genetics Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Cancer Genetics Risk Assessment and Counseling are:

• Kathleen A. Calzone, PhD, RN, AGN-BC, FAAN (National Cancer Institute)
• Suzanne M. O'Neill, MS, PhD, CGC
• Beth N. Peshkin, MS, CGC (Lombardi Comprehensive Cancer Center at Georgetown University Medical Center)
• Susan K. Peterson, PhD, MPH (University of Texas, M.D. Anderson Cancer Center)
• Susan T. Vadaparampil, PhD, MPH (H. Lee Moffitt Cancer Center & Research Institute)
• Catharine Wang, PhD, MSc (Boston University School of Public Health)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Cancer Genetics Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Cancer Genetics Editorial Board. PDQ Cancer Genetics Risk Assessment and Counseling. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/causes-prevention/genetics/risk-assessment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389258]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.

• Updated: November 8, 2019