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Cancer Genetics Risk Assessment and Counseling (PDQ®)

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The Option of Genetic Testing

Factors to Take into Consideration in Offering Testing
        Indications for testing
        Value of testing an affected family member first
        Testing in families with a documented deleterious mutation
        Genetic testing and assisted reproductive technology
Determining the Test to be Used
        Regulation of genetic tests
Direct-to-Consumer (DTC) Marketing of Genetic Tests
        Trends in DTC marketing of genetic tests
        DTC genetic testing in children
        Concerns about marketing of DTC genetic tests
        Research examining the impact of DTC marketing of genetic tests
Informed Consent
        Core elements of informed consent
        Testing in children
        Testing in vulnerable populations
Importance of Pretest Counseling
Psychological Impact of Genetic Information/Test Results on the Individual
Psychological Impact of Genetic Information/Test Results on the Family
        Exploration of potential risks, benefits, burdens, and limitations of genetic susceptibility testing
        Posttest education and result notification

Factors to Take into Consideration in Offering Testing

Indications for testing

Experts recommend offering genetic testing when a risk assessment suggests the presence of an inherited cancer syndrome for which specific genes have been identified. The American Society of Clinical Oncology (ASCO) Policy Statement on Genetic Testing for Cancer Susceptibility proposes that genetic testing be offered when the following conditions apply:

  • An individual has a personal or family history suggestive of a genetic cancer susceptibility syndrome.
  • The results of the test can be interpreted.
  • Testing will influence medical management.[1,2]

Characteristics used in making this determination are discussed in the PDQ summaries on the genetics of specific cancers. Even when individual and family history characteristics indicate a possible inherited cancer syndrome, individuals may elect not to proceed with testing after discussion of potential risks, benefits, and limitations, as discussed below. Conversely, individuals whose pedigrees are incomplete or uninformative due to very small family size, early deaths, or incomplete data on key family members may elect to pursue genetic testing in an attempt to better define their risk status. In these situations, it is particularly important that the pretest counseling fully explore the limitations of the testing process.

In 2010, ASCO updated its policy statement to address testing for low- to moderate-penetrance genes, multiplex genomic tests, and direct-to-consumer (DTC) testing. This current ASCO framework (Table 1) recommends that the provider consider the evidence for clinical utility of the test in addition to whether the test was obtained through a health care provider or directly by the consumer.[2]

Table 1. Clinical Utility of Genetic/Genomic Testsa
Test Ordered By Clinical Utility Accepted Clinical Utility Uncertain  
aAdapted from Robson et al.[2]
Health care ProfessionalHigh-penetrance gene mutations (i.e., BRCA1, BRCA2)Low- and moderate-penetrance gene mutations (e.g., CHEK2)
ConsumerHigh-penetrance gene mutations (i.e., BRCA1, BRCA2)Low- and moderate-penetrance gene mutations

ASCO’s position is that when a test, regardless of clinical utility, is ordered by a health care professional, the provider is responsible for organizing follow-up care based on the findings. For tests that were ordered by the consumer without health care professional involvement, management decisions are based on the evidence for clinical utility. For tests with accepted clinical utility, follow-up care can be guided by the evidence for cancer risk associated with the genetic test finding. However, in tests ordered by the consumer that have uncertain clinical utility, ASCO recommends that follow-up care consist of education regarding the lack of evidence regarding the test's clinical utility and that cancer risk management decisions be guided by established cancer risk factors.[2]

Genetic education and counseling, including the interpretation of genetic test results, will vary depending on whether a previous attempt at genetic testing has been made (see Figure 2). In general, there are two primary circumstances in which genetic testing is performed:

  • Families with evidence of an inherited susceptibility that have not had any genetic testing or in which genetic testing has not identified a mutation.
  • Families with a documented deleterious mutation.
Flowchart showing a multi-step genetic testing algorithm for testing for cancer susceptibility.
Figure 2. This genetic testing algorithm depicts the multistep process of testing for cancer susceptibility.
Value of testing an affected family member first

Genetic susceptibility testing generally yields the most useful information when a living family member affected with the cancer of concern is tested first to determine whether a genetic basis for the cancer diagnosis can be established. Three possible outcomes for this form of testing include the following (see Figure 2):

If a mutation that is documented to be deleterious (associated with cancer risk) is identified, risks are based on penetrance data for mutations of that specific gene. In addition, other family members may be tested for the presence or absence of this specific mutation. If no mutation is found in an affected family member, testing is considered uninformative and thus there is no basis for testing unaffected relatives. Failure of the laboratory to detect a mutation in an affected family member does not rule out an inherited basis for the cancer in that family. Reasons why testing could be uninformative include the following:

  • The cancer in the family may be associated with a cancer susceptibility gene other than the gene that was tested.

  • The cancer in the family may be associated with a gene mutation, but the cancer in the specific family member who underwent testing is not associated with that mutation. This can occur especially with cancers that are common in the general population, such as breast cancer or prostate cancer. The family member who is affected with the disease but is not a carrier of the mutated gene associated with the inherited predisposition to cancer in the family is considered a phenocopy.

  • Identifying a gene mutation may not be possible given the limited sensitivity of the laboratory techniques used to detect mutations. There may be additional testing available to detect certain types of mutations that would have been missed by the initial genetic test.

  • The function of the gene could be altered by a mutation in a different gene.

Lastly, testing may reveal a variant of uncertain significance. This result means that a gene mutation has been found; however, the extent that this mutation increases cancer risk, or whether it is associated with the history of cancer in the family, is uncertain. In this circumstance, some clues as to the significance of the mutation can be derived from the following:

  • The location of the mutation in relation to regions and function of a gene.

  • The specific change; since many variants are missense mutations, not all amino acid substitutions are as significant.

  • Whether the variant has been documented in the presence of a documented deleterious mutation.

  • Whether the mutation is associated with the branch in the family with the cancer and/or whether the variant tracks with the cancers in the family.

Unfortunately, even with this information, there is often insufficient evidence to document the significance of a specific variant, and further clarifying research is required.

If there is no close, living, affected relative to undergo testing, or the living affected relative declines testing, other options may be discussed with the patient and the testing laboratory. These generally involve weighing the availability and reliability of testing the stored tissue of a deceased relative or testing an unaffected person without prior testing of an affected family member. Tests done on stored tissue are technically difficult and may not yield a definitive result. Testing an unaffected person without prior testing of an affected relative often is uninformative because a negative test does not rule out the presence of a cancer susceptibility gene in the family or the subject.

Testing in families with a documented deleterious mutation

Genetic susceptibility testing for a documented deleterious mutation in the family can be very informative and will yield one of the following two results (see Figure 2):

  • Positive for the familial mutation.
  • Negative for the familial mutation.

If the familial mutation is detected in a family member, their cancer risks are based on penetrance data for mutations in that specific gene. If the documented mutation is not found in a family member, the risk of cancer in that individual is equivalent to cancer risk in the general population. However, other risk factors and family history from the side of the family not associated with the documented mutation may increase the cancer risk above the general population levels.

In summary, genetic education and counseling includes identifying the most informative person in the family to test, which may be an affected family member rather than the individual seeking genetic services. In addition, counseling includes a discussion of the limitations of the test, all possible test outcomes, and the consequences of identifying a variant of unknown clinical significance.[3]

Genetic testing and assisted reproductive technology

Advances in reproductive technology have enabled predisposition cancer genetic testing to be performed in the prenatal setting using chorionic villus sampling and amniocentesis and in the preimplantation setting using preimplantation genetic diagnosis.[4-6] A literature review coupled with a brief survey found 55 case reports of prenatal or preimplantation diagnosis performed for cancer predisposition for more than 12 familial cancer syndromes.[4] In a telephone survey of 13 centers listed in an online resource as providing preimplantation genetic diagnosis, nine reported they provided this service for cancer predisposition syndromes.[4]

Reproductive medicine used in the context of predisposition genetic testing for cancer risk raises important ethical, legal, and social issues. A proposed analytic framework recommends considering the following issues:

  1. Does the cancer syndrome include childhood malignancies or significant morbidity or mortality at an early age?
  2. What is the penetrance associated with the gene mutation?
  3. How severe is the syndrome phenotype?
  4. Are there interventions available that decrease the mutation-associated cancer risk or are proven to detect cancer early when it is in a treatable form?[5]

When counseling cancer susceptibility gene mutation carriers who are considering childbearing, it is important to address the issues listed above while maintaining sensitivity to the potential parents' personal beliefs.[5]

Determining the Test to be Used

Genetic testing is highly specialized. A given test is usually performed in only a small number of laboratories. There are also multiple molecular testing methods available, each with its own indications, costs, strengths, and weaknesses. Depending on the method employed and the extent of the analysis, different tests for the same gene will have varying levels of sensitivity and specificity. Even assuming high analytic validity, genetic heterogeneity makes test selection challenging. A number of different genetic syndromes may underlie the development of a particular cancer type. For example, hereditary colon cancer may be due to familial adenomatous polyposis (FAP), Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, or other syndromes. Each of these has a different genetic basis. In addition, different genes may be responsible for the same condition (e.g., Lynch syndrome can be caused by mutations in one of several mismatch repair [MMR] genes).

In some genes, the same mutation has been found in multiple, apparently unrelated families. This observation is consistent with a founder effect, wherein a mutation identified in a contemporary population can be traced back to a small group of founders isolated by geographic, cultural, or other factors. For example, two specific BRCA1 mutations (185delAG and 5382insC) and one BRCA2 mutation (6174delT) have been reported to be common in Ashkenazi Jews. Other genes also have reported founder mutations. The presence of founder mutations has practical implications for genetic testing. Many laboratories offer directed testing specifically for ethnic-specific alleles. This greatly simplifies the technical aspects of the test but is not without limitations. For example, approximately 15% of BRCA1 and BRCA2 mutations that occur among Ashkenazim are nonfounder mutations.[7] Also, for genes in which large genome rearrangements are founder mutations, ordering additional testing using different techniques may be needed.

Allelic heterogeneity (i.e., different mutations within the same gene) can confer different risks or be associated with a different phenotype. For example, though the general rule is that adenomatous polyposis coli (APC) gene mutations are associated with hundreds or thousands of colonic polyps and colon cancer of the classical FAP syndrome, some APC mutations cause a milder clinical picture, with fewer polyps and lower colorectal cancer risk.[8,9] In addition, other disorders may be part of the FAP spectrum. Mutations in a certain portion of the APC gene also predispose to retinal changes, for example, when mutations in a different region of APC predispose to desmoid tumors. Thus, selection of the appropriate genetic test for a given individual requires considerable knowledge of genetic diagnostic methods, correlation between clinical and molecular findings, and access to information about rapidly changing testing options. These issues are addressed in detail in PDQ summaries on the genetics of specific cancers. (Refer to the PDQ summaries on Genetics of Breast and Ovarian Cancer; Genetics of Colorectal Cancer; and Genetics of Endocrine and Neuroendocrine Neoplasias for more information.)

Regulation of genetic tests

Government regulation of genetic tests to date remains extremely limited in terms of both analytic and clinical validity with little interagency coordination.[10] The Centers for Medicare & Medicaid Services, using the Clinical Laboratory Improvement Act (CLIA), regulates all clinical human laboratory testing performed in the United States for the purposes of generating diagnostic or other health information. CLIA regulations address personnel qualifications, laboratory quality assurance standards, and documentation and validation of tests and procedures.[11] For laboratory tests themselves, CLIA categorizes tests based on the level of complexity into waived tests, moderate complexity, or high complexity. Genetic tests are considered high complexity, which indicates that a high degree of knowledge and skill is required to perform or interpret the test. Laboratories conducting high complexity tests must undergo proficiency testing at specified intervals, which consists of an external review of the laboratory's ability to accurately perform and interpret the test.[10,12] However, a specialty area specific for molecular and biologic genetic tests has yet to be established; therefore, specific proficiency testing of genetic testing laboratories is not required by CLIA.[10]

In regard to analytic validity, genetic tests fall into two primary categories; test kits and laboratory-developed tests (previously called home brews). Test kits are manufactured for use in laboratories performing the test and include all the reagents necessary to complete the analysis, instructions, performance outcomes, and details about which mutations can be detected. The U.S. Food and Drug Administration (FDA) regulates test kits as medical devices; however, despite more than 1,000 available genetic tests, there are fewer than ten FDA-approved test kits.[12] Laboratory-developed tests are performed in a laboratory that assembles its own testing materials in-house; [12] this category represents the most common form of genetic testing. Laboratory-developed tests are subject to the least amount of oversight, as neither CLIA nor the FDA evaluate the laboratories' proficiency in performing the test or clinical validity relative to the accuracy of the test to predict a clinical outcome.[10,12] The FDA does regulate manufactured analyte-specific reagents (ASRs) as medical devices. These small molecules are used to conduct laboratory-developed tests but can also be made by the laboratory. ASRs made in the laboratory are not subject to FDA oversight. For laboratory-developed tests utilizing manufactured commercially available ASRs, the FDA requires that the test be ordered by a health professional or other individual authorized to order the test by state law. However, this regulation does not distinguish between health providers caring for the patient or health providers who work for the laboratory offering the test.[12]

In addition to classical clinical genetic tests is the regulatory oversight of research genetic testing. Laboratories performing genetic testing on a research basis are exempt from CLIA oversight if the laboratory does not report patient-specific results for the diagnosis, prevention, or treatment of any disease or impairment or the assessment of the health of individual patients.[10] However, there are anecdotal reports of research laboratories providing test results for clinical purposes with the caveat that the laboratory recommends that testing be repeated in a clinical CLIA-approved laboratory. In addition, there is no established mechanism that determines when a test has sufficient analytic and clinical validity to be offered clinically.[12] Currently, the decision to offer a genetic test clinically is at the discretion of the laboratory director.

Evidence regarding the implications of this narrow regulatory oversight of genetic tests is limited and consists predominately of laboratory director responses to quality assurance surveys. A survey of 133 laboratory directors performing genetic tests found that 88% of laboratories employed one or more American Board of Medical Genetics (ABMG)-certified or ABMG-eligible professional geneticists, and 23% had an affiliation with at least one doctoral-prepared geneticist. Eight percent of laboratories did not employ and were not affiliated with doctoral-level genetics professionals. Laboratory-developed tests were performed in 70% of laboratories. Sixty-three percent of laboratories provided an interpretation of the test result as part of the test report.[13] Another survey of 190 laboratory directors found that 97% were CLIA-certified for high complexity testing. Sixteen percent of laboratories reported no specialty area certification; those without specialty certification represented laboratories with the most volume of tests performed and offered the most extensive test selection.[10] Of laboratories with specialty certification, not all had certification relevant to genetic tests, with 48% reporting pathology certification, 46% chemistry certification, and 41% clinical cytogenetics certification. Sixteen percent of directors reported participation in no formal external proficiency testing program, although 77% performed some informal proficiency testing when a formal external proficiency testing program was not available.

The most frequent reason cited for lack of proficiency testing participation was lack of available proficiency testing programs. Laboratory directors estimated that in the past 2 years 37% issued three or fewer incorrect reports, and 35% issued at least four incorrect reports. Analytic errors such as faulty reagent, equipment failure, or human error, increased 40% with each decrease in level of proficiency training completed.[10] An international genetic testing laboratory director survey involving 18 countries found that 64% of the 827 laboratories that responded accepted samples from outside their country.[14] Similar to the U.S. study, 74% reported participation in some form of proficiency testing. Fifty-three percent of the laboratories required a copy of the consent to perform the test, and 72% of laboratories retained specimens indefinitely that were submitted for testing.[14]

The U.S. Department of Health and Human Services Secretary’s Advisory Committee on Genetics, Health, and Society has published a detailed report regarding the adequacy and transparency of the current oversight system for genetic testing in the United States. The Committee identified gaps in the following areas:

  • Regulations governing clinical laboratory quality.
  • Oversight of the clinical validity of genetic tests.
  • The number and identification of laboratories performing genetic tests and the specific genetic tests being performed.
  • Level of current knowledge about the clinical usefulness of genetic tests.
  • Educational preparation in genetics of health providers, the public health community, patients, and consumers.
Direct-to-Consumer (DTC) Marketing of Genetic Tests

Over the last decade there has been a marked increase in companies advertising or providing genetic services directly to the consumer.[15-17] Accordingly, it is inevitable that an increasing number of patients will approach physicians and genetic counselors armed with information or genetic test results from DTC companies. In the next sections, information is provided about: (1) trends in DTC marketing of genetic tests; (2) concerns about DTC marketing of genetic tests; and (3) research examining the impact of DTC marketing of genetic tests.

Trends in DTC marketing of genetic tests

In 2002, a search of Internet-based studies found 14 genetic testing companies advertising adult health-related susceptibility testing, with only three companies actually offering testing directly to the public.[15,16] A 2005 and 2006 study identified 24 Internet-based companies providing DTC testing.[17] The companies surveyed offered diverse types of testing, including diagnostic tests for single high-penetrance diseases, such as Huntington disease; risk assessment tests for polygenic diseases, such as breast cancer and Alzheimer disease; and testing for many low penetrance genes that may have ramifications for health or well being, such as nutrigenomic or nutrigenetic tests or cardiovascular profiles. About one-quarter (24%) offered diagnostic and risk assessment tests; 21% offered all genetic tests; 21% offered enhancement tests only; 17% offered risk assessment and enhancement tests; 13% offered diagnostic tests only; and one company (4%) offered risk assessment tests only. The investigators for this study defined enhancement test as a test for one or more low-penetrance genes for the purpose of providing information on general aspects of health, nutrition, and/or treatment regimens, such as nutrigenetic or pharmacogenetic tests and cardiovascular health profiles. This study also examined the content of the Internet information and found that companies offering diagnostic and risk assessment tests were much more likely to indicate that a physician associated with the company would be involved in interpreting the tests than companies offering enhancement testing. Of these companies, eight did not require a physician to be involved in ordering tests or interpreting the results.[17] More than 75% of the 24 companies stated that they recommended or provided phone-based genetic counseling services. When genetic counseling was offered by the company, there was no information provided about the qualifications of the counselors and the scope of the information and counseling provided.

DTC genetic testing in children

One study identified 48 DTC companies and was able to contact 37 of them between December 2009 and April 2010 regarding participation in a survey about their company policies for testing children. Thirteen of the 37 companies participated in the survey, despite guarantees of confidentiality. Ten of 13 (77%) companies reported that they allowed genetic testing of minors; of these ten, nine reported receiving requests to test minors from parents or legal guardians. One company reported receiving a direct request from a minor to be tested. The investigators did not collect data on the types of tests the DTC companies provide; however, the implication is that most of the tests offered evaluate genetic susceptibility to adult-onset disorders.[18]

Concerns about marketing of DTC genetic tests

Several professional organizations have released position statements or recommendations cautioning against DTC advertising and provision of genetic tests. The main concerns that are expressed within these statements include the following:

  1. Patients may lack knowledge in key areas, such as the purpose and appropriateness of testing, accuracy, follow-up implications, clinical significance of results for themselves and other family members, or the reliability of the laboratory.

  2. The lack of required health care provider involvement and the lack of stated qualifications of the health care providers utilized by the companies themselves directs the onus on the patients to interpret complex findings or to take the initiative to seek other opinions.

  3. The lack of adequate regulatory oversight of laboratory tests documenting the analytic and clinical validity and clinical utility prior to test availability.[19]

In 2004, The American College of Medical Genetics Board of Directors asserted that genetic testing for susceptibility to disease are medical tests; therefore, these tests should be provided to the public through qualified health care professionals only. Given the complexities of genetic testing and counseling, telephone or Internet orders of home testing kits may be harmful because of the potential for inappropriate test use, misinterpretation of results, and lack of follow-up.[20] More recently, the American Society of Human Genetics (ASHG) [21] provided a policy statement on DTC genetic testing, citing the need for broader oversight of laboratory assessments by the FDA and Federal Trade Commission (FTC) in order to ensure reliable tests. The ASHG statement [21] recommended a series of standards in the area of transparency, provider education, and test and laboratory quality, and concluded that further research and federal oversight are needed in this rapidly changing field. In 2006, the FTC and Centers for Disease Control and Prevention issued a joint statement to consumers regarding the limitations of DTC genetic tests.

Proponents of DTC marketing and provision of genetic tests often assert the putative "right to information," which they argue promotes patient autonomy.[22] DTC marketing may increase patients’ feelings of empowerment to discuss their care with their physicians. Patients may also 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.[23] While the issue of privacy is also emphasized in DTC marketing and testing claims, it may not be as salient after testing, given that those found to be positive will, for the most part, want their physician involved early in identifying measures to mitigate risk.[24]

Research examining the impact of DTC marketing of genetic tests

Marketing of DTC genetic tests includes diverse strategies for increasing awareness and market demand for genetic testing services by for-profit companies. There are two approaches to targeting consumers with information about DTC genetic tests. The first is called DTC advertising, which promotes the availability of a genetic test to the public but requires involvement of a health care provider to order the test and disseminate the results to the consumer. The second approach, DTC genetic testing, is discussed below.[25] While numerous position papers, review articles, and commentaries have been published, there are few empirical examples about the impact of DTC advertising of genetic tests on patients, providers, or the health care system. The most studied example to date is the Myriad Genetics campaign to increase awareness of BRCA1/2 mutation testing through multiple mass media outlets (print, radio, and television). In 2002, Myriad launched its first DTC marketing campaign in Denver and Atlanta. The target audience for this campaign was women from the general population aged 25 to 54 years. In May 2002, Myriad began with educational outreach to providers in the two cities in anticipation of patient requests for information spurred by the DTC campaign, which ran from September 2002 to February 2003. The campaign included television, radio, and print advertisements that were expected to reach greater than 90% of the target audience an average of 16 times during the 5-month period.[26,27] Subsequently, these DTC campaigns have been conducted in the northeast, Texas, and Florida. These campaigns were immediately criticized for providing incomplete, manipulative information.[28,29]

Empirical research was conducted immediately following the 2002 campaign. A random digit dialing survey of 1,635 women in the campaign cities (Denver and Atlanta) and two control cities found increased levels of awareness of BRCA1/2 genetic testing in target cities.[30] However, no significant differences were observed in perceived knowledge about testing, concern about breast cancer, or interest in testing. There was no evidence that knowledge was differentially increased in those women with strong family histories of breast cancer, who would most benefit from consideration of testing.[30] No overall increase in anxiety or confusion about testing was reported. Of women who reported exposure to the DTC advertisement, 63% reported no anxiety at all, and 76% reported no confusion.[26] A smaller study of 315 women from the Denver area found that women at increased risk of breast cancer were more knowledgeable about BRCA testing and more likely to recall the advertisement. However, an equal number of high and low risk women felt they would benefit from genetic testing and were interested in testing.[31] A consumer survey based on a cross-sectional, stratified, random sample of at-risk women explored the effects of socioeconomic status (SES) on women’s reactions to a BRCA1/BRCA2 genetic testing DTC marketing campaign.[32] The survey was conducted at two intervention sites (n = 811) and two control sites (n = 824), and knowledge of the genetic test, perceptions of personal risk, communications with others about the test, and interest in pursuing the test were evaluated. SES, as measured by income and education, had no differential effect on any of the outcome measures in women at the intervention sites and control sites. However, the study did report a consistent overall effect of SES on most variables measured, independent of the intervention site. For example, women of lower SES reported being less knowledgeable about genetics and risk, yet were more interested in genetic testing. These results suggest that SES could play a role in access to genetic services, how women understand their genetic risk of inherited breast and ovarian cancer susceptibility, and what they do about it.

The impact of the advertising campaign on physicians was also a focus of investigation. Physicians in target cities were more likely to remember hearing an advertisement for testing but did not have increased knowledge compared with physicians in control cities. Physicians in target cities reported increases in patients’ questions about genetic testing, genetic counseling referrals, and requests for testing.[30,33] In summary, physicians might have been more likely to make a referral for testing based on the patient’s interest in testing, whether or not the doctor is informed enough to consider whether the test is appropriate. The most concerning documented problem with this campaign was that the company targeted the general population, even though genetic testing for BRCA1/2 is only appropriate for a subgroup of women.[26]

In addition to the data from the Myriad campaign, one international study examined the impact of a DTC campaign for genetic testing by a group of researchers in partnership with a popular Polish women’s magazine (Twoj Styl). Genetic testing was offered to 5,000 women through an announcement placed in Twoj Styl in October 2001. A total of 5,024 women who qualified received a free genetic test for three BRCA1 mutations that are common in Poland. Genetic counseling was offered only to women with a positive test or with a significant family history of breast or ovarian cancer. The great majority of women who took part in the program expressed a high degree of satisfaction, and after 1 year, approximately two-thirds of identified mutation carriers had complied with breast cancer screening recommendations.[34] No follow-up with women who received a negative test result to assess understanding of their results was conducted nor was subsequent follow-up conducted regarding population screening recommendations.

Research examining DTC testing

DTC genetic testing is advertised directly to consumers, purchased directly by the consumer, and the results are delivered directly to the consumer without the involvement of the consumer’s health care provider.[25] Some might suggest that DTC genetic tests promise heightened privacy and the potential that individuals will be more informed and more able to take an active, decision-making role in their medical options.[35]

DTC laboratories predominantly rely on Web material to disseminate test information to consumers. One study evaluated how using a Web-based decision tool that provided information about a multiplex genetic susceptibility test influenced participants’ testing decisions.[36] The Web-based tool was developed specifically for the study by an interdisciplinary research team and was designed using principles of health literacy, communication, and prior research. The tool implemented a layered menu approach that allowed participants to select the order and amount of content viewed. Participants included 526 members of a large Midwestern health maintenance organization ranging in age from 25 to 40 years with no evidence of any of the health conditions included in the test. Participants most frequently viewed the Web pages describing the test, testing procedures, and implications of the results and less frequently viewed the pages about specific health conditions or genes. Participants viewed an average of eight Web pages (mean 8.2, standard deviation 7.2, range 1–27), including an average of 2.9 of the 4 pages introducing the multiplex test, 2.2 of the 8 pages describing the health conditions on the test, and 3.2 of the 15 pages describing the genes, out of a possible 27 total pages. The number of Web pages viewed was significantly associated with ease of decision making (odds ratio, 1.04; 95% CI, 1.01–1.07).

There is growing interest in trying to use genetic information to guide decisions about healthy lifestyle, including dietary choice, although there is no evidence base for implementing such practices. A 2006 study of consumer and physician awareness of DTC nutrigenomic tests found that 14% of consumers and 44% of physicians had heard of the tests, but actual utilization was exceedingly low (0.6% of consumers had used one).[37] This study examines awareness of nutrigenomic testing in Michigan, Oregon, and Utah via the 2006 Behavioral Risk Factors Surveillance System. Awareness was highest in Oregon (24.4%) and Utah (19.7%) and lowest in Michigan (7.6%). Those who had higher incomes, greater education, and increasing age (except those older than 65 years) were more aware of nutrigenomic tests.[38] Of those consumers who had heard of DTC nutrigenomic tests, 46% had heard about them from television, 35% from magazines, 29% from newspapers, and only 13% from health professionals. There was great variation in the extent to which background information concerning the disease in question was presented. For example, more than half of these companies offered information about disease etiology, but far fewer offered information about diagnosis and treatment or prevention. Companies providing tests of little clinical utility (such as enhancement tests) tended to provide more detailed information, although the information provided about the diseases and genetics in general was not always accurate, as clinical validity claims were supported by peer-reviewed literature in only approximately half the companies. The trend identified in this survey of available companies indicates that the tests with the least clinical utility are provided with the least professional oversight and counseling services.

A study of 1,087 users of Facebook, a social-networking Web site, who proactively registered with a marketing firm indicated that almost half of respondents were aware of personal genetic testing (PGT).[39] Fewer than 10% of respondents had used PGT for a variety of conditions, including, but not limited to, cancer; however, the majority indicated that they would consider using PGT (64%). The study also identified key areas in which individuals may benefit from additional education and information. For example, one-third of respondents mistakenly understood that the PGT results indicated a diagnosis of disease as opposed to risk of developing disease. In addition, respondents viewed physicians as an important resource in understanding and using PGT results to make health care decisions.

Another study examined how 145 Facebook users interpreted DTC information. Participants completed an online survey in which separate scenarios containing information derived from DTC Web sites about the risk of developing heart disease, colorectal cancer, or basal cell skin cancer were presented. The authors found that even in this highly educated cohort, of whom 56% were in the health care field, the reported ease of understanding the test results was not related to an accurate interpretation of the results.[40] Of those who answered that the results were easy or very easy to understand for each of the scenarios, correct interpretation varied greatly (59%–80%) across the four scenarios.

A study offered DTC genomic risk assessments at reduced cost to 3,640 highly educated (90% had some college or more), high-income (median, $100,000–$149,000 per year), predominantly white (80%) employees in the health care (the sponsoring institution), technology, and biotechnology fields.[41] Those who declined participation were more likely to be nonwhite. Among those who underwent DTC testing, about half (49.7%) expressed testing-related concerns; the most frequently cited concerns involved privacy issues. In multivariate analyses, female gender, employment in a health care field, younger age, higher education, and higher trait anxiety were significant predictors of expressing concerns about testing. The majority (82.4%) indicated that they would want to know their genetic risk of a nonpreventable disease. Women, whites, those who were younger, those who were in health-related occupations, and those who had higher trait anxiety expressed more uncertainty about whether they would want to know their genetic risk of a nonpreventable disease.

Of the 56% of participants who provided a 3-month follow-up assessment, there was neither evidence of clinically meaningful distress and health behavior change (dietary fat intake, exercise) nor a statistically significant difference in screening test uptake compared with baseline measures. Illness-specific worry was not assessed. Only 10% of participants had discussed their test results with a DTC company-specific genetic counselor; only 27% had discussed their results with their physician.[42]

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.[43] This view is driven by several ethical dilemmas that can arise in genetic susceptibility testings. 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.[44] 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.[45] 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,[2,46,47] 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, variant of uncertain significance, inconclusive, false positive).
  • 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 (see below) 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 testing results become available.

Testing in children

Genetic testing for mutations in cancer susceptibility genes in children is particularly complex. While both parents [48] and providers [49] 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 years or older) because of concerns about autonomy, potential discrimination, and possible psychosocial effects.[50-52] 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).[53,54] As a consequence, decisions about genetic testing in children are made in the context of a specific gene in which a mutation 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.[1,2] 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 mutations). The decision to test in such circumstances is particularly controversial.[1,2]

Special considerations are required when genetic counseling and testing for mutations 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.[1,2,55] Counseling under these circumstances incorporates a discussion of how test results will be shared with the child when he or she is older.[1,2] Children aged 10 to 17 years may have more involvement in the decision-making process.[56] 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.[56] 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.[55] 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.[55] 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.[55] 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.[57,58]

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.[1,2] 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 Ovarian Cancer; 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 mutations.)

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.[51] 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 Genetics 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.[59] 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.[60] For example, New York State guidelines specify that “When an increased risk for hereditary susceptibility is identified through the individual or family history, the clinician should initiate discussion or refer the patient for information concerning genetic testing and its potential benefits and burdens. The clinician who opts to take on this responsibility must provide the depth of content and time required to ensure that the patient can make an informed testing choice.”[46]

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.[61-63] 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.[64-68] 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 following 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.[69] 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.[70,71]

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.[72,73]

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,[74] the Profile of Mood States,[75] the Hospital Anxiety and Depression Scale,[76] and the Brief Symptom Inventory.[77] 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.[78]

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.

In addition to using a pedigree to evaluate family health history, tools such as the genogram and ecomap can provide specific information regarding the nature of interpersonal relationships within the family and the connections with social networks outside of the family.[79-81]

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 mutation 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.[82]

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 Ovarian Cancer and Genetics of Colorectal Cancer for more information.)

Exploration of potential risks, benefits, burdens, and limitations of genetic susceptibility testing

There is substantial evidence that many people do not understand the potential limitations of genetic testing and may give too much weight to the potential benefits.[83-85] Counseling provides the opportunity to present a balanced view of the potential risks and benefits of testing and to correct misconceptions. It may be helpful to ask individuals to identify their perceptions about the pros and cons of testing as part of this discussion.

  1. Potential burdens of a test result that is uninformative or of uncertain significance.

    In the absence of a known mutation in the family, a negative test result is not informative. In this situation, the tested person’s risk status remains the same as it was prior to testing. One study of 183 women with an uninformative BRCA test result found that most women understood the implications of the test result, and it did not alter their intention to undergo a high-risk screening regimen.[86,87] If the test identifies a new mutation of unknown clinical significance, the test result is of uncertain significance and cannot be used to revise the tested person’s risk estimate. Subsequent research, however, may provide information about the mutation’s effect (or lack of effect) on cancer risk.

    Potential burdens

    • Need to evaluate other family members to determine the significance of mutations not known to be disease related.
    • Persistent uncertainty about risk status, which may result in a recommendation for intensive monitoring if a hereditary predisposition cannot be ruled out with certainty.
    • Lack of evidence-based guidance regarding prevention or surveillance strategies.
    • Continuing anxiety, frustration, and other adverse psychological sequelae associated with uncertainty because no definitive answer has been provided.
    • High monetary cost of testing.
  2. Potential benefits and burdens of a positive test in an unaffected, at-risk individual when a disease-related mutation has been previously identified in the family.

    Potential benefits

    • Elimination of uncertainty about inherited susceptibility for an individual.
    • Potential for reduction in future morbidity and mortality through enhanced cancer risk management strategies (i.e., increased screening, adoption of a healthy lifestyle, and avoidance of risk factors).
    • Opportunity to reduce cancer risk through chemoprevention and risk-reducing surgery.
    • Opportunity to inform relatives about the likelihood that they have the family mutation and about the availability of genetic testing, cancer risk assessment, and management services.

    Potential burdens

    • Neglect of screening and surveillance resulting from increased anxiety about being a mutation carrier.
    • Psychological distress, including anxiety, depression, reduced self-esteem.
    • Increased worry about cancer due to unproven effectiveness of current interventions to reduce risk.
    • Risks and costs of increased screening or prophylaxis.
    • Strained/altered relationships within family.
    • Guilt about possible transmission of genetic risk to children.
    • Potential insurance, employment, or social discrimination.
  3. Potential benefits and burdens of a negative test result when a disease-related mutation has been identified in the family.

    Potential benefits

    • Reassurance and reduction of anxiety about personal cancer risk due to heredity.
    • Avoidance of unnecessary intensive monitoring and prevention strategies.
    • Avoidance of aggressive interventions such as risk-reducing surgery.
    • Relief that children are not at increased risk.

    Potential burdens

    • Neglect of routine surveillance resulting from misunderstanding of a negative test result. The patient remains at the general population risk and may be at increased risk depending on his or her personal risk factors and any risk associated with the other branch of the family.
    • Adjustment to the change in expected life course.
    • Survivor guilt.
    • Strained relationship with others in family.
    • Regret over previous decisions (e.g., having had risk-reducing surgery prior to being tested).
  4. Potential benefits and burdens of a positive test result in an individual who is the first identified mutation carrier in a family.[3]

    Potential benefits

    • No need to rely on other family members for informative test results.
    • Potential for risk reduction in future morbidity and mortality through enhanced cancer risk management strategies (i.e., increased screening and surveillance, chemoprevention, and risk-reducing surgery).
    • Opportunity to inform relatives about the likelihood that they have the family mutation and about the availability of genetic testing, cancer risk assessment, and management services.

    Potential burdens

    • Confronting ethical dilemmas about who should receive the information, what should be conveyed, and when it should be conveyed to specific family members.
    • Coping with potential personal distress in conveying the information.
    • Coping with family members' potential distress and reaction to the information.
    • Feeling unprepared for the tasks associated with disseminating genetic information through the family.
    • Loss of privacy.
    • Coping with potential personal psychological distress and reaction to the information.
Posttest education and result notification

The primary component of the posttest session is result notification. An individual may change his or her mind about receiving results, however, until the moment of results disclosure. Therefore, one typically begins the disclosure session by confirming that test results are still desired. Some people may decline or delay receipt of test results. The percentage of people who will make this decision is unknown. Such people need ongoing follow-up and the opportunity to receive test results in the future.

Once confirmed, people appreciate direct, immediate reporting of the results; they often describe the wait for results as one of the most stressful aspects of undergoing testing.[88] Often, people need a few minutes of privacy to gather their composure after hearing their test results. Sometimes this precludes all but the briefest discussion at the initial posttest visit. Usually, individuals who have been properly prepared through the pretest counseling process do not exhibit disabling distress. Although it is rare that an acute psychological reaction will occur at disclosure, it is useful for providers of genetic test results to establish a relationship with a mental health provider who can be consulted should extreme reactions occur or who can be available by referral for people seeking further exploration of emotional issues.

Either at the time of disclosure or shortly thereafter, a session for the provider and the individual to consider the genetic, medical, psychological, and social ramifications of the test result is advisable. Despite having extensive pretest education, people may still be confused about the implications and meaning of the test results. Examples of frequently documented misconceptions include the belief that a positive result means that cancer is present or certain to develop; the belief that a negative result means that cancer will never occur; and failure to understand the uncertainty inherent in certain test results, as when only a limited mutation panel was examined. Regarding medical implications, it is important to inform the person of risk implications and management options for all of the cancer types associated with an inherited syndrome and to revisit options for risk management.

Posttest counseling may include consideration of the implications of the test results for other family members. It has been suggested that some individuals affected by an inherited disorder agree to have genetic testing performed in order to acquire information that could be shared with family members. There is evidence that implementation of a follow-up counseling program with the index patient, after test results are revealed, will significantly increase the proportion of relatives informed of their genetic risk. Follow-up counseling may include telephone conversations with the index patient verifying which family members have been contacted and an offer to assist with conveying information to family members.[89] Some experts have suggested that if a test result is positive, plans should be made at this time for the notification, education, and counseling of other relatives based on the test result of the individual. Written materials, brochures, or personal letters may aid people in informing the appropriate relatives about genetic risk.

When a test result is negative, the posttest session may be briefer. It is important, however, to discuss genetic, medical, and psychological implications of a negative result in a family with a known mutation. For example, it is essential that the person understand that the general population risks for relevant cancer types still apply and that the person’s individual risk of cancer may still be influenced by other risk factors and family history from the other side of the family. Furthermore, people may be surprised to feel distress even when a test is negative. This outcome has been documented in the context of BRCA1/2 mutation testing [90] and may also be anticipated in other cancer susceptibility testing. Posttest results discussion of such distress may lead to referral for additional counseling in some cases.

Many individuals benefit from follow-up counseling and consultation with medical specialists after disclosure of test results. This provides an opportunity for further discussion of feelings about their risk status, options for risk management including screening and detection procedures, and implications of the test results for other family members.

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