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Patients and clinicians alike view anonymous testing as a potential way to avoid perceived risks of genetic testing such as insurance and employment discrimination and the potential loss of privacy. To assess their experience with and attitudes towards anonymous testing for BRCA1/2, genetic counselors were invited to complete an internet-based survey via the NSGC Familial Cancer Risk Counseling Special Interest Group (FCRC-SIG) listerv. A majority of the 115 respondents (70%) had received requests from patients for anonymous BRCA1/2 testing at some point in their careers and 43% complied with this request. Most counselors, however, encountered such requests infrequently, 1-5 times per year. Although genetic counselors do not generally encourage anonymous testing and over a third of respondents feel it should never be offered, a substantial subset support its use under specific circumstances. In general, a strong consensus exists among counselors that anonymous testing should not be offered routinely. In light of the current legislative landscape, it is of note that a substantial proportion of respondents (42.7%) cited the threat of life insurance discrimination as a reason for pursuing AT, and fewer cited health insurance (30.0%) or employment discrimination (29.1%) as justifications. Since there exists no federal legislative protections against discrimination by life insurance companies, it makes sense that genetic counselors were more responsive to this issue as opposed to the threat of discrimination in health insurance and employment.

Background: Warfarin is a mainstay of therapy for conditions associated with an increased risk of thromboembolic events. However, the use of this common agent is fraught with complications and little is known regarding inter-individual variation in warfarin response. Objective: We tested for association between single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 and average weekly warfarin dose required to maintain patients at their desired anticoagulation target. Methods: The sample consisted of 93 European-American patients from anticoagulation clinics at the University of North Carolina at Chapel Hill. Data on mean weekly warfarin dose were collected over a mean treatment period of 20.6 months. ANCOVA models were used and haplotype analysis was performed. Results: Three of six VKORC1 SNPs were found to be very strongly associated with the average warfarin dose required to achieve the target international normalised ratio (INR; p

Background: Lower enrolment of minorities into research studies has been reported frequently. Most studies have little information about nonparticipants, making it difficult to identify characteristics associated with enrolment and how they might vary by race. Methods: Women who had previously participated in a population-based, case-control study of breast cancer in North Carolina were invited to enrol in a cancer genetics registry. Detailed questionnaire data on sociodemographic characteristics and cancer risk factors were available for all women. We compared characteristics of women who agreed to be in the registry with those who were deceased, were unlocatable, or declined enrolment. Unconditional logistic regression analyses were done to identify predictors of enrolment. Results: Enrolment rates were markedly lower among African Americans than Whites (15% and 36%, respectively) due to both lower contact rates (41% versus 63%) and lower enrolment rates among those contacted (37% versus 58%). Logistic regression models suggested that racial differences in enrolment were not due to socioeconomic characteristics or other cancer risk factors; race was the only significant predictor of enrolment in multivariable models (odds ratio 0.41, 95% confidence interval 0.23-0.72). Conclusions: Although all women had previously taken part in a research study, African American women were less likely to enrol in the cancer genetics registry than White women. A possible explanation of these findings is that studies of genetics may present particular concerns for African Americans. Further research is needed to identify attitudes and issues that present barriers to participation among minorities.

The incomplete penetrance of mutations in BRCA1 and BRCA2 suggests that some combination of environmental and genetic factors modifies the risk of breast cancer in mutation carriers. This study sought to identify possible interactions between established breast cancer risk factors and BRCA1 or BRCA2 mutations using a case-only study design. Breast cancer cases that had been tested for BRCA1 and BRCA2 mutations were identified from 11 collaborating centers. Comparisons of reproductive and lifestyle risk factors were made between women with breast cancer who were positive for BRCA1 mutations (n = 283), BRCA2 mutations (n = 204), or negative for both BRCA1 and BRCA2 mutations (n = 894). Interaction risk ratios (IRRs) were calculated using multinominal logistic regression models. Compared with non-carriers, statistically significant IRRs were observed for later age at menarche among BRCA2 mutation carriers, for a greater number of pregnancies among both BRCA1 and BRCA2 mutation carriers, and for alcohol use among BRCA1 mutation carriers. Our data suggest that the risk for breast cancer among BRCA1 or BRCA2 carriers may be modified by reproductive characteristics and alcohol use. However, our results should be interpreted cautiously given the overall inconsistency in the epidemiologic literature on modifiers of BRCA1 and BRCA2.

While the traditional model of genetic evaluation for breast cancer risk recommended face-to-face disclosure of genetic testing results, BRCA1/2 testing results are increasingly provided by telephone. The few existing studies on telephone genetic counseling provide conflicting results about its desirability and efficacy. The current study aimed to (1) Estimate the prevalence among genetic counselors of providing BRCA1/2 genetic test results by phone (2) Assess patient satisfaction with results delivered by telephone versus in-person. A survey was sent to members of the Familial Cancer Risk Counseling Special Interest Group via the NSGC listserve and was completed by 107 individuals. Additionally, 137 patients who had received BRCA genetic testing results either by phone or in-person at UNC Chapel Hill Cancer Genetics Clinic were surveyed regarding satisfaction with the mode of their BRCA1/2 results delivery. The genetic counseling survey revealed that the majority of responding counselors (92.5%) had delivered BRCA1/2 genetic test results by telephone. Patients having received results either in person or by phone reported no difference in satisfaction. Most patients chose to receive results by phone and those given a choice of delivery mode reported significantly higher satisfaction than those who did not have a choice. Those who waited less time to receive results once they knew they were ready also reported higher satisfaction. This study found supportive results for the routine provision of BRCA1/2 genetic test results by telephone. Results suggest that test results should be delivered as swiftly as possible once available and that offering patients a choice of how to receive results is desirable. These are especially important issues as genetic testing becomes more commonplace in medicine.

This study explored whether reactions to the Cancer Genetics Network (CGN) or CGN enrollment differed by receipt of a standard informational brochure versus a targeted version addressing factors previously associated with African Americans’ health behavior decisions and research participation. The 262 participants, identified through tumor registries or clinic contacts, were mailed brochures and completed phone interviews. When asked whether – based on the brochure – they were or were not ‘leaning toward’ CGN enrollment, about 75% of both standard and targeted groups reported leaning toward. When given the opportunity at the end of the interview, 68% enrolled in the CGN. Trust was strongly related to enrollment. Less education, less satisfaction with cancer care, and individualistic rather than collective orientation were associated with lower trust. Education was also bivariately associated with enrollment, but mediation analysis indicated that the operational mechanism of education’s influence on enrollment was through trust.

PurposeStudies suggest that African American women are less likely to pursue BRCA1/2 genetic testing than white women. However, such studies are often confounded by unequal access to care.MethodsData from 132 African American and 636 white women, obtained from a clinical database at the University of North Carolina (Chapel Hill, NC) between 1998 and 2005, were analyzed to assess BRCA1/2 genetic testing uptake. Importantly, the clinical setting minimized barriers of both cost and access. Race and time of new breast cancer diagnosis (recent v > 1 year before genetic evaluation) were assessed for association with BRCA1/2 testing uptake using multivariable logistic regression models.ResultsBoth race (P = .0082) and a recent diagnosis of breast cancer (P = .014) were independently associated with testing uptake. African American women had a lower estimated odds of pursuing testing than white women (odds ratio [OR], 0.54; 95%CI, 0.34 to 0.85), and women with a recent diagnosis had a higher OR than those with a remote diagnosis (OR, 1.58; 95% CI, 1.10 to 2.29). In a race-stratified analysis, there was no statistical evidence for association between recent status and testing uptake in the larger white stratum (OR, 1.38, P = .13) while there was for the smaller African American sample (OR, 2.77, P = .018). The test of interaction between race and remote status was not significant (P = .15).ConclusionAfrican American race was associated with an overall decreased uptake of BRCA1/2 genetic testing, even when barriers of ascertainment and cost were minimized. However, among African American women, a recent diagnosis of breast cancer was associated with substantially increased uptake of testing.

While many individual risk factors have been defined for breast cancer, a family history was recognized long ago as one of the most potent. Mutations within BRCA1 or BRCA2, both identified about 10 years ago, are responsible for the majority of inherited breast cancer. By virtue of her age alone, a young woman diagnosed with breast cancer has a greatly elevated probability to carry a BRCA mutation. Other risk factors, including a personal or family history of ovarian cancer, bilateral breast cancer or Jewish ancestry, only serve to increase that chance. It is critical that clinicians caring for a young woman understand their patient's elevated risk to carry such a mutation and thoughtfully investigate this risk. Upon identification of a mutation in a young woman there are many consequences which necessitate careful consideration of various treatment and preventative options including prophylactic mastectomy and oophorectomy. Finally, the diagnosis of breast cancer in a young woman and the attendant genetic implications have immediate and serious consequences for her family members. Genetic professionals can help navigate the complex technical and psychosocial issues. This chapter explores the molecular, clinical and ethical intricacies of BRCA genetic testing.

Family-based research is essential to understanding the genetic and environmental etiology of human disease. The success of family-based research often depends on investigators' ability to identify, recruit, and achieve a high participation rate among eligible family members. However, recruitment of family members raises ethical concerns due to the tension between protecting participants' privacy and promoting research quality, and guidelines for these activities are not well established. The Cancer Genetics Network Bioethics Committee assembled a multidisciplinary group to explore the scientific and ethical issues that arise in the process of family-based recruitment. The group used a literature review as well as expert opinion to develop recommendations about appropriate approaches to identifying, contacting, and recruiting family members. We conclude that there is no single correct approach, but recommend a balanced approach that takes into account the nature of the particular study as well as its recruitment goals. Recruitment of family members should be viewed as part of the research protocol and should require appropriate informed consent of the already-enrolled participant. Investigators should inform prospective participants why they are being contacted, how information about them was obtained, and what will happen to that information if they decide not to participate. The recruitment process should also be sensitive to the fact that some individuals from families at increased genetic risk will have no prior knowledge of their risk status. These recommendations are put forward to promote further discussion about the advantages and disadvantages of various approaches to family-based recruitment. They suggest a framework for considering alternative recruitment strategies and their implications, as well as highlight areas in need of further empirical research.

Lower enrolment of minorities into research studies has been reported frequently. Most studies have little information about nonparticipants, making it difficult to identify characteristics associated with enrolment and how they might vary by race.Women who had previously participated in a population-based, case-control study of breast cancer in North Carolina were invited to enroll in a cancer genetics registry. Detailed questionnaire data on sociodemographic characteristics and cancer risk factors were available for all women. We compared characteristics of women who agreed to be in the registry with those who were deceased, were unlocatable, or declined enrolment. Unconditional logistic regression analyses were done to identify predictors of enrolment.Enrolment rates were markedly lower among African Americans than Whites (15% and 36%, respectively) due to both lower contact rates (41% versus 63%) and lower enrolment rates among those contacted (37% versus 58%). Logistic regression models suggested that racial differences in enrolment were not due to socioeconomic characteristics or other cancer risk factors; race was the only significant predictor of enrolment in multivariable models (odds ratio 0.41, 95% confidence interval 0.23-0.72).Although all women had previously taken part in a research study, African American women were less likely to enroll in the cancer genetics registry than White women. A possible explanation of these findings is that studies of genetics may present particular concerns for African Americans. Further research is needed to identify attitudes and issues that present barriers to participation among minorities.

Cardiac ryanodine receptor (RYR2) and Kir2.1 (KCNJ2) mutations are a cause of catecholaminergic polymorphic ventricular tachycardia (CPVT), a lethal cardiac channelopathy. Here, we describe mutations in RYR2 and KCNJ2 in patients referred for FAMILION CPVT genetic testing. Sequence analysis of 38