Risk Genetic Testing Research Articles

Prenatal Diagnosis, Preimplantation Genetic Diagnosis, and Cancer: Was Hamlet Wrong?

Prenatal Diagnosis, Preimplantation Genetic Diagnosis, and Cancer: Was Hamlet Wrong?

Effect of Genetic Testing for Risk of Alzheimer's Disease

Genetic testing can be considered a complex variant of diagnostic testing. If the results are not actionable, the findings may lead to anxiety or even life-disrupting actions with little offsetting benefit. Even if the results are actionable, the anxiety or actions resulting from disclosure may outweigh any benefit. Because the benefits of genetic testing are often modest, and the tests themselves are often imprecise in identifying risk, consideration must be given to potential harm in revealing the test results. A test that discloses an elevated risk of Alzheimer's disease — a fearsome condition involving memory loss, personality change, and physical . . .

What Can Interest Tell Us about Uptake of Genetic Testing? Intention and Behavior amongst Smokers Related to Patients with Lung Cancer

Background: Much of the research examining psychosocial aspects of genetic testing has used hypothetical scenarios, based on the largely untested assumption that hypothetical genetic testing intentions are good proxies for behavior. We tested whether hypothetical interest predicts uptake of genetic testing and whether factors that predict interest also predict uptake. Methods: Participants (n = 116) were smokers and related to patients with lung cancer, who completed a telephone survey. Interest in genetic testing for lung cancer risk was indicated by responding ‘definitely would’ to a Likert-style question. Internet-delivered genetic testing for lung cancer risk was then offered. Uptake was indicated by requesting the test and receiving the result. Results: 63% of participants said they ‘definitely would’ take the genetic test; uptake was 38%. Participants who said they ‘definitely would’ take the test were more likely than others to take the offered test (45% vs. 26%, p = 0.035). Interest was associated with attitudes towards genetic testing and motivation to quit smoking. Uptake was associated with motivation, prior awareness of genetic testing, and daily Internet use. Conclusion: Hypothetical interest only modestly predicts uptake of genetic testing. Interest in genetic testing likely reflects generally positive attitudes that are not good predictors of the choices individuals subsequently make.

Men at Increased Risk of Developing Breast Cancer: Language Preferences for Naming a Cancer-Related Mutation

Patients attending familial cancer clinics may find the term "mutation" offensive and potentially stigmatizing, yet there is little consensus in the literature as to the most appropriate alternative terms to describe a cancer-related mutation to individuals considering genetic testing for cancer risk. This study aimed to describe a cancer-related mutation in a rare group of familial cancer clinic patients: men at increased risk of carrying a breast cancer-related mutation. Twenty-seven men completed a self-report questionnaire that assessed their preferences for language to describe a cancer-related mutation. Overall, men were most likely to spontaneously suggest the term "faulty gene" to describe a cancer-related mutation when asked an open-ended question about their language preferences. When asked to rate the term "faulty gene" in comparison to the terms "altered gene," "mutation," "nonworking gene," "malfunctioning gene," and "gene change," the term "faulty gene" received the highest mean preference rating in this sample of men at increased risk of developing breast cancer. This area of investigation remains controversial and would benefit from more formal and larger-scale investigations of the language preferences of individuals at increased risk of developing cancer.

Guidelines for Genetic Risk Assessment of Hereditary Breast and Ovarian Cancer: Early Disagreements and Low Utilization

BRCA1/2 testing is one of the most well-established genetic tests to predict cancer risk. Guidelines are available to help clinicians determine who will benefit most from testing. To identify women at high risk of hereditary breast and ovarian cancer and estimate their awareness of and experience with genetic testing for cancer risk. Analyses of the 2000 and 2005 National Health Interview Surveys. Women with no personal history of breast or ovarian cancer (n = 35,116). Risk of hereditary breast or ovarian cancer based on self-reported family history of cancer and national guidelines; self-reported awareness of genetic testing for cancer risk; discussion of genetic testing for cancer risk with a health professional; having undergone genetic testing for breast/ovarian cancer risk. Using guideline criteria, 0.96% of women were identified as being at high risk of hereditary breast and ovarian cancer. Among high-risk women, 54.04% were aware of genetic testing for cancer risk, 10.39% had discussed genetic testing with a health professional, and 1.41% had undergone testing for breast/ovarian cancer risk. Adjusting for survey year, high-risk women were more likely than average-risk women to have heard of genetic testing for cancer risk (RR, 1.3, 95% CI 1.2-1.4), to have discussed genetic testing with a health professional (RR 5.2, 95% CI 3.6-7.4), and to have undergone genetic testing for breast/ovarian cancer risk (RR 6.8, 95% CI 2.6-18.0). We find low provision of guideline-recommended advice to women for whom testing may be appropriate and of significant clinical benefit.

Biomarkers in prostate cancer diagnosis and prognosis: beyond prostate-specific antigen

To review the most recent advances in genetic testing for prostate cancer risk and of new molecular diagnostic assays to improve diagnostic accuracy and treatment decision beyond prostate-specific antigen (PSA) testing. Multiple independent studies had demonstrated evidence that genetic variations in three regions of chromosome 8q24 and one each at 17q12 and 17q24.3 are independent predictors of prostate cancer risk in addition to family history and serum PSA levels. The small percentage of individuals with several anomalies can have up to 10 times the risk of prostate cancer. Novel molecular urine tests have been studied, and the prostate cancer antigen 3 RNA detection has been studied most extensively and is now commercially available. It provides an independent and synergistic information to predict a higher or lower risk of prostate cancer at given PSA level and can further help predict the tumor volume and Gleason grade found on the prostatectomy specimen. Sensitivity of the prostate cancer antigen 3 test could be improved by the detection of the fusion gene transcripts transmembrane protease serine 2-E26 transformation specific-related gene and serine peptidase inhibitor Kazal type 1 who may in addition allow the identification of prostate cancer patients at higher risk of life-threatening disease. The challenge in the years to come will be to introduce these new gene-based diagnostic and prognostic tests in algorithms integrating the other known risk factors of age, ethnicity, family history and PSA level to better tailor diagnostic and therapeutic strategies.

Genetic testing for melanoma risk: a prospective cohort study of uptake and outcomes among Australian families

PurposeThe aim of this prospective cohort study was to examine uptake and psychological, behavioral, and cognitive outcomes of genetic testing for melanoma risk among individuals with a known family-specific CDKN2A mutation. MethodsA total of 119 individuals were ascertained via a genetic epidemiological study and completed a series of mailed, self-administered questionnaires at multiple time points, including notification of genetic test availability, and 2 weeks and 12 months after receipt of genetic test results (for “test participants”), or 12 months after notification (for “decliners”). ResultsSince January 2005, 21% of participants (n = 25) have undergone genetic testing, with 75% of those who have received results identified as mutation carriers (n = 15). Factors associated with uptake of genetic counseling included perceived susceptibility to melanoma (odds ratio = 3.60, P = 0.0008), and fatalistic beliefs about melanoma (odds ratio = 0.57, P = 0.005). Compared with baseline, carriers reported significantly reduced anxiety scores at 2 weeks, and reduced depression scores at 2 weeks and 12 months, after receipt of genetic test results. Carriers also reported a significantly greater frequency of clinical skin examination at 12-month follow-up compared with decliners (χ2 = 5.70, P = 0.02). No hypothesis testing was carried out for noncarriers because of their limited number. ConclusionThese data provide preliminary evidence for healthy psychological, behavioral, and cognitive adjustment after participation in genetic testing for melanoma risk.

Coping With Genetic Testing for Breast Cancer Susceptibility

To examine how women cope with genetic testing for heightened susceptibility to breast cancer. Participants were 126 White women (age = 44 +/- 9 years) who were participants in a larger study of genetic testing for risk of different chronic diseases. All women were at higher-than-average risk for breast cancer due to a personal and/or family history and were considering genetic testing. Distress (Symptom Checklist-90-Revised, Impact of Event Scale, Perceived Stress Scale, Spielberger State-Trait Anxiety Inventory, and the Center for Epidemiological Studies Depression Scale) was assessed at four assessments; one before and three after the decision to have genetic testing. The majority of women (n = 100) had testing. The follow-up assessments occurred at 1 week after receiving results (or 3-4 months after baseline if testing was not elected), and then at 3 and 6 months after the second assessment. Coping (Brief COPE) was measured at the first and third assessments. Coping was relatively stable over time and did not vary as a function of genetic test results. Active coping strategies were used more often by women with a personal cancer history than by women without cancer. Use of avoidant coping was reliably and positively associated with distress over time independent of cancer history and test result. The identification of specific coping styles that were associated with more or less distress is useful as a means of identifying and targeting coping interventions and predicting which participants may be at risk for distress.

The influence of acculturation and breast cancer‐specific distress on perceived barriers to genetic testing for breast cancer among women of African descent

Rising health disparities are increasingly evident in relation to use of genetic services (including genetic counseling and testing) for breast cancer risk, with women of African descent less likely to use genetic services compared with Whites. Meanwhile, little is known regarding potential within-group acculturation and psychological differences underlying perceived barriers to genetic testing among women of African descent. Hypothesized contributions of acculturation factors and breast cancer-specific distress to perceived barriers to genetic testing were examined with a statistical analysis of baseline data from 146 women of African descent (56% US born and 44% foreign born) meeting genetic breast cancer risk criteria and participating in a larger longitudinal study that included the opportunity for free genetic counseling and testing. Perceived barriers assessed included: (1) anticipation of negative emotional reactions, (2) stigma, (3) confidentiality concerns, (4) family-related worry, and (5) family-related guilt associated with genetic testing. In multivariate analyses, being foreign born was a significant predictor of anticipated negative emotional reactions about genetic testing (beta=0.26; SE=0.11; p=0.01). Breast cancer-specific distress scores (avoidance symptoms) were positively related to anticipated negative emotional reactions (beta=0.02; SE=0.005; p=<0.0001), confidentiality concerns (beta=0.02; SE=0.01; p=0.02), and family-related guilt (beta=0.02; SE=0.01; p=0.0009) associated with genetic testing. Results suggest an influence of acculturation and breast cancer-specific distress on perceived barriers to genetic testing among women of African descent. The potential utility of culturally tailored genetic counseling services taking into account such influences and addressing emotional and psychological concerns of women considering genetic testing for breast cancer should be investigated.

Development and Pilot Testing of a Decision Aid for Men Considering Genetic Testing for Breast and/or Ovarian Cancer–Related Mutations (BRCA1/2)

Despite the fact that both men and women can carry a breast/ovarian cancer-related mutation, the main emphasis in genetic counseling for breast/ovarian cancer-related risk remains on females. This study aimed to develop and pilot a decision aid specifically designed for men with a strong family history of breast and/or ovarian cancer who are considering genetic testing. The decision aid was developed by a multidisciplinary team of experts and a consumer representative. It was then reviewed by 27 men who had previously undergone genetic testing to identify a mutation in a BRCA1 or BRCA2 gene. All men who reviewed the decision aid indicated that they would recommend the booklet to other men in the same situation, and 96% of the sample (n = 26) reported being "very satisfied" or "satisfied" with the information contained in the decision aid. The decision aid was perceived by all participants as "very relevant" or "quite relevant" for men considering genetic testing. Ninety-three percent of men felt that it was easy to weigh the pros and cons of genetic testing with the help of the decision aid. The perceived impact on participants' emotions and understanding of the genetic testing process was also assessed. Several factors may hinder men from effectively weighing up the potential benefits and risks of genetic testing. A greater understanding of these issues may help health professionals to encourage men with a strong family history of breast and/or ovarian cancer to learn about cancer risk and the appropriate management strategies for themselves and their female relatives.

Randomized trial of a decision aid for individuals considering genetic testing for hereditary nonpolyposis colorectal cancer risk

Despite the potential benefits of genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) risk, individuals can find the genetic testing decision-making process complicated and challenging. The goal of the current study was to measure the effectiveness of a tailored decision aid designed specifically to assist individuals to make informed decisions regarding genetic testing for HNPCC risk. In all, 153 individuals were randomized to receive the decision aid or a control pamphlet at the end of their first genetic counseling consultation. Of these, 109 (71.2%) completed the first questionnaire 1 week after consultation, whereas 95 (62.1%) completed the 6-month follow-up questionnaire. Although the decision aid had no significant effect on postdecisional regret or actual genetic testing decision, the trial results demonstrated that participants who received the decision aid had significantly lower levels of decisional conflict (ie, uncertainty) regarding genetic testing (chi-square(1) = 8.97; P = .003) and were more likely to be classified as having made an informed choice concerning genetic testing (chi-square(1) = 4.37; P = .037) than participants who received a control pamphlet. Also, men who received the decision aid had significantly higher knowledge levels regarding genetic testing compared with men who received the control pamphlet, whereas no such differences were found for women (chi-square(2) = 6.76; P = .034). A decision aid for individuals considering genetic testing for HNPCC is an effective intervention to reduce uncertainty and assist individuals to make an informed choice regarding genetic testing for HNPCC after genetic counseling.

Acculturation and Familiarity With, Attitudes Towards and Beliefs about Genetic Testing for Cancer Risk Within Latinas in East Harlem, New York City

Recent research underscores the need for increasing use of genetic testing for cancer risk in Latinos. This study examined the influence of acculturation on attitudes, beliefs about and familiarity with genetic testing for cancer risk in a community-based sample of Latinas in East Harlem, New York City (N = 103). Multivariate linear regression models analyzed the relationship of acculturation to: (1) familiarity (2) perceived benefits (3) perceived barriers and (4) concerns about abuses of genetic testing for cancer risk. Controlling for sociodemographic factors, results revealed that with increasing acculturation Latinas were more familiar with genetic testing (beta = 1.62, SE = 0.72, p = 0.03), more likely to cite perceived benefits (beta = 1.67, SE = 0.79, p = 0.04), and less likely to report perceived barriers related to genetic testing (beta = -2.76, SE = 1.64, p = 0.10). Study results may help inform the development of culturally-appropriate health education outreach materials and programs targeted to increase awareness, knowledge and understanding about genetic testing for cancer risk within Latinas.

Adolescent Medical Providers' Willingness to Recommend Genetic Susceptibility Testing for Nicotine Addiction and Lung Cancer Risk to Adolescents

To examine the influences of disease, lifestyle, and other factors on adolescent medical providers' willingness to recommend genetic susceptibility testing (GST). Providers attending a national conference completed a self-report survey (n = 232) about their willingness to recommend hypothetical GSTs, differentiated by disease (nicotine addiction/lung cancer), patient lifestyle (nonsmoker/smoker), and other contextual factors. Compared to recommending GST unconditionally, providers were more willing to recommend GST with parental/patient consent/assent, and in the presence of a preexisting illness and substance abuse history. Compared to offering nicotine addiction GST to a nonsmoker, providers were more willing to offer this type of testing to a smoker and were more willing to offer GST for lung cancer regardless of patient lifestyle. Providers' willingness to recommend GSTs is sensitive to many factors. Efforts to integrate GST into adolescent preventive care likely will need to address these and other influences on provider behavior.

Psychological distress and quality of life associated with genetic testing for breast cancer risk

This study investigated short- and long-term psychological outcomes associated with BRCA1/2 genetic testing in women with a personal or family history of breast cancer. Participants included 126 women considering genetic testing. Questionnaires were administered prior to testing, one week, three and six months after result disclosure. Results indicated no systematic effects of testing based on personal cancer history. Mutation carriers and women who elected not to be tested reported greater perceived risk and intrusive and avoidant thoughts at follow-up time points than did women who received negative (uninformative) or variant results. Mutation carriers reported more distress at the three-month follow-up but by six months the effects of test result on distress dissipated and groups were comparable. Cluster analyses identified two groups of individuals based on distress at baseline; these groups were used to predict psychological outcomes after testing. Distress remained constant in both groups: those who were high at baseline remained high and those who were low remained low. Test results did not moderate this effect. Results suggest that genetic testing for BRCA1/2 does not increase distress or have deleterious effects on quality of life over the long term. However, sub-groups of women may report more distress over time. These data indicate the need for more targeted counseling to individuals who report high levels of distress when considering genetic testing.

Attitudes Toward Genetic Testing for Cancer Risk after Genetic Counseling and Decision Support: A Qualitative Comparison between Hereditary Cancer Types

This study aimed to qualitatively assess individuals' attitudes toward genetic testing for cancer risk after genetic counseling and decision support. As part of a larger study, 78 women considering genetic testing for hereditary breast/ovarian cancer (HBOC) risk and 22 individuals considering genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) completed an open-ended table of their perceived pros and cons of genetic testing. The most frequently reported pros were "to help manage my risk of developing cancer," "to help my family," and "to know my cancer risk." With regards to risk management, the HBOC group perceived genetic testing as most helpful in informing their general risk management practices, while the HN-PCC group focused on the potential to clarify their need for bowel cancer screening, suggesting that patients' perceptions of the benefits of genetic testing may differ across cancer syndromes. Individuals in both groups expressed concern about the potential psychological impact of genetic testing. We also found that some affected individuals may not fully comprehend the meaning of their potential test results. Eliciting patients' perceived pros and cons during genetic counseling is likely to be a valuable tool for improving patient care. This data also provides an improved evidence base for the development of patient education tools.

International Perspectives on Genetic Counseling and Testing for Breast Cancer Risk

Familial cancer services have been developed in many countries in response to a rapidly evolving demand for genetic counseling and testing for breast cancer risk. This article presents a synthesis of the literature on international aspects of genetic counseling and testing and discusses similarities and differences in the provision of genetic counseling and testing, taking seven countries with well established familial cancer services as a case study (Australia, Canada, France, Germany, Netherlands, UK and US). Potential international differences are discussed in terms of: provider and patient attitudes to genetic counseling and genetic testing; utilization rates of genetic testing and prophylactic surgery; and the psychological impact of genetic testing for breast cancer risk. The comparative analyses of utilization rates and the psychological impact of testing indicate a wide range of variability in uptake rates and psychological outcomes, most likely reflecting sample variability and methodological differences in measurement. International comparison studies using controlled designs would be required to ascertain whether international differences exist, and to disentangle the differential role of clinical, individual and family context factors, on the one hand, and the cultural and health system-related factors unique to particular countries, on the other.

Usefulness of the Threatening Medical Situations Inventory in individuals considering genetic testing for cancer risk

Objective To assess the psychometric properties of the Threatening Medical Situations Inventory (TMSI) in a community sample (Study 1), and to examine its usefulness in individuals with a strong family history of cancer (Study 2). Methods Study 1 participants ( N = 276) completed 2 online surveys, 14 days apart. Study 2 participants ( N = 311) completed 2 questionnaires, 6 months apart. Results Both studies revealed the inventory was psychometrically sound, although some concerns were raised about the factor structure. High monitors in Study 1 reported desiring more health-related information and an active role in medical decision-making. High monitors in Study 2 had the greatest knowledge increase when they received a detailed decision aid, compared to a brief pamphlet. Conclusion The TMSI is appropriate for use in both community and clinical samples. High monitors in the general community are more likely to prefer receiving as much health-related information as possible and desire an active role in decision-making about their health. Practice implications Familial cancer clinic patients may benefit from tailoring the amount of information they receive to their coping style, such that patients who are vigilant information-seekers may benefit most from receiving more detailed information about genetic testing.

Valuing personalized medicine: willingness to pay for genetic testing for colorectal cancer risk.

Personalized medicine using genetic information is increasing in cancer screening and treatment; however, little is known about perceived value of genetic testing for cancer risk in a general population. The objectives of this report are: to identify a general population's willingness to pay for genetic testing that provids colorectal cancer risk information; examine whether screening intentions (likelihood of testing and test choice) change based on risk; and identify providers' beliefs about patients' perceived value. A survey of US general (n=1087) and physician (n=100) populations using the willingness-to-pay method was carried out. Physicians responded from the perspective of a typical patient. χ2 tests, t-tests and ordered logistic regression were used to examine factors associated with willingness to pay and intentions to be screened. General population respondents' average willingness to pay for a genetic test for colorectal cancer risk was US$150. Higher willingness to pay was significantly associated with being male, having higher income and education, having private health insurance and reporting a greater likelihood of getting colorectal cancer screening when due. Physicians' beliefs about patients were different than general population responses: physicians believed patients would be willing to pay more (US$212; p<0.001), fewer believed patients would not pay (1vs 17%; p<0.001), and if a genetic test indicated higher than average risk, physicians believed patients would be more likely to get screened (65 vs 46%; p<0.001) and would choose alternative screening tests (62 vs 22%; p<0.001). Respondents valued genetic tests to inform screening decisions and indicated that tests may influence screening choices. Additional studies are needed to examine the implications of physicians' beliefs about patients' choices for screening.

High‐ and average‐risk individuals' beliefs about, and perceptions of, malignant melanoma: an Australian perspective

Despite expanding knowledge regarding the genetics of melanoma, there have been few attempts to define the psychosocial experiences of individuals with a family history of this disease. This study explored the ways in which individuals at varying levels of risk perceive, and respond to, melanoma. Forty semi-structured interviews were undertaken with affected (n = 20) and unaffected (n = 20) individuals with or without a family history of melanoma. Data were analysed for potential thematic differences between risk groups, genders, and intentions to pursue genetic testing for melanoma risk. Overall, participants with a family history were in acceptance of their increased risk status and had developed ways of coping without major disruption to their daily lives. However, some participants expressed ambiguity regarding the causes of melanoma and the effectiveness of health behaviours such as sun protection. Major thematic patterns identified for those intending to pursue genetic testing were: negative emotional associations with melanoma; an emphasis on screening and sun avoidance, but not sun protection; and heightened perceptions of personal susceptibility to melanoma. In contrast, thematic patterns identified for those likely to decline testing were: ready access to stories of melanoma survival; and an emphasis on the causal role of sun exposure, whilst still believing that genetic factors may contribute to melanoma susceptibility. Compared to males, females reported a greater tendency to completely avoid the sun in order to reduce their melanoma risk. The data provide preliminary evidence for the importance of identifying misconceptions that may impede informed decision-making about genetic testing for melanoma risk.

Genetic testing for heart disease susceptibility: potential impact on motivation to quit smoking

As genetic tests for common gene variants and multifactorial, lifestyle-related conditions become available, it will be increasingly important to determine the psychological and behavioral impact of this emerging class of genetic tests. Our aim was to examine the potential impact of genetic testing for heart disease susceptibility on psychological predictors of smoking cessation. Two hundred and sixty-one smokers were asked to imagine that they had undergone a test for heart disease risk. They were randomly assigned to a genetic test scenario (low- or high-risk result) or an oxidative test scenario (high-risk result). Smokers in the genetic test-high risk group reported greater intention to quit smoking than smokers in the oxidative test-high risk group (p = 0.009); 30% of this was mediated by their holding stronger beliefs that quitting would reduce their heart disease risk (outcome expectations) (p = 0.011). The effect of genetic test-high risk feedback on outcome expectations was greatest amongst smokers with no heart disease family history (p = 0.038). The results suggest that genetic testing for heart disease risk may enhance interventions designed to improve health via increasing smoking cessation rates. Whether the findings hold true in studies that use real rather than hypothetical genetic tests remains to be seen.