Barbara B. Biesecker

Psychological distress in women seeking genetic counseling for breast-ovarian cancer risk: The contributions of personality and appraisal

The purpose of the present study was two-fold: (a) to characterize the psychological status of women with a family history of breast or ovarian cancer who self-refer for genetic counseling and BRCA1 testing; and (b) to identify specific demographic, personality, and appraisal factors that contribute to cancer-specific distress and general distress in this group of women. Participants were 256 women ages 18 and older who had at least one first-degree relative (FDR) with breast and/or ovarian cancer. Participants were recruited through breast cancer clinics and obstetrics/gynecology departments at two medical centers by responding to program information described in a brochure. The results revealed moderate distress levels in this population. The results of a hierarchical regression of general distress indicated that women with higher levels of general distress were less likely to be married, less optimistic, and had heightened breast cancer risk perceptions accompanied by feelings of low perceptions of control over the development of breast cancer (R2=.44, p=.0001). Women with higher levels of cancer-specific distress tended to be younger and non-White and had low perceptions of control over developing breast cancer (R2=.15, p=.0002). These findings suggest that self-referred genetic counseling participants may be psychologically vulnerable and may benefit from interventions designed to decrease distress and the perceived absence of control over developing breast cancer.

Ethics and Genomic Incidental Findings

Laboratories have an obligation to report clinically beneficial incidental findings. The American College of Medical Genetics and Genomics (ACMG) recently issued a statement (1) recommending that all laboratories conducting clinical sequencing seek and report pathogenic and expected pathogenic mutations for a short list of carefully chosen genes and conditions. The recommendations establish a baseline for reporting clinically relevant incidental findings and articulate ethical principles relevant to their disclosure. The ACMG acknowledged that the list will evolve over time and is developing a mechanism for community input (2). This paper focuses on the ethical framework for the recommendations, rather than on the choice of which genes to include on the list.

Goals of genetic counseling

The goals of genetic counseling have differed over the past three decades. Two schools of thought are prominent in reviewing past literature. One upholds the goal of preventing birth defects and genetic disorders while the other promotes a goal of improved psychological well‐being in client adaptation to a genetic condition or risk. Both types of goals emphasize that clients should make their own reproductive decisions; however, the former relies on clients making decisions that will reduce the impact of genetic disorders. The differences in the types of goals may be due to the training and orientation of genetics health care providers, socio‐cultural views, or priorities of health care settings. Regardless, there are ample reasons to dismiss the prevention of birth defects as a goal. This mini‐review recommends use of genetic counseling sub‐specialties as a framework for considering different client needs and thus different counseling goals and specific aims in the reproductive, pediatric/adult, and common disease settings. Given the extent of new genetic information, technologies, and the need to evaluate genetic counseling practice, genetics health care providers should work toward arriving at consensus on the goals of genetic counseling, and in doing so, the needs of clients should be considered.

Psychosocial factors predicting BRCA1/BRCA2 testing decisions in members of hereditary breast and ovarian cancer families.

Although BRCA1/2 testing has increasingly entered clinical practice, much is to be learned about the most effective ways to provide counseling to persons potentially interested in receiving test results. The purpose of this study was to identify factors affecting genetic testing decisions in a cohort of hereditary breast and ovarian cancer (HBOC) families presented with the choice to undergo testing. Relatives in these families are known to carry BRCA1 or BRCA2 mutations. Sociodemographics, personality traits, and family functioning were self-assessed using validated psychometric instruments at baseline. Among 172 individuals who participated in pretest education and counseling, 135 (78%) chose to undergo genetic testing and 37 (22%) chose not to be tested. Individuals who chose to undergo genetic testing were more likely to be older (> or =40 years), to have lower levels of optimism, and to report higher levels of cohesiveness in their families. A better understanding of factors that influence interest in predictive testing may help to inform the counseling that occurs prior to genetic testing.

Intentions to receive individual results from whole-genome sequencing among participants in the ClinSeq study

Genome sequencing has been rapidly integrated into clinical research and is currently marketed to health-care practitioners and consumers alike. The volume of sequencing data generated for a single individual and the wide range of findings from whole-genome sequencing raise critical questions about the return of results and their potential value for end-users. We conducted a mixed-methods study of 311 sequential participants in the NIH ClinSeq study to assess general preferences and specific attitudes toward learning results. We tested how these variables predicted intentions to receive results within four categories of findings ranging from medically actionable to variants of unknown significance. Two hundred and ninety-four participants indicated a preference to learn their genome sequencing results. Most often, participants cited disease prevention as their reason, including intention to change their lifestyle behaviors. Participants held positive attitudes, strongly perceived social norms and strong intentions to learn results, although there were significant mean differences among four categories of findings (P<0.01). Attitudes and social norms for medically actionable and carrier results were most similar and rated the highest. Participants distinguished among the types and quality of information they may receive, despite strong intentions to learn all results presented. These intentions were motivated by confidence in their ability to use the information to prevent future disease and a belief in the value of even uninterpretable information. It behooves investigators to facilitate participants’ desire to learn a range of information from genomic sequencing while promoting realistic expectations for its clinical and personal utility.

The future of genetic counselling: an international perspective

The focus of clinical genetics, and thus genetic counselling, is forecast to expand from the diagnosis and prediction of rare, often untreatable conditions, to the prediction of common, often treatable or preventable conditions1. Whether this evolution is likely to proceed rapidly or at a pace that permits sensible integration of molecular genetic tools is unknown and a source of debate2,3. It is clear, however, that genetic discoveries will modify the way in which disease and risk are conceptualized. Here, we predict how genetic counselling, specifically for more common diseases, might be provided in the decades to come. We envisage an expansion of professional roles and expertise for many health care providers and highlight the need for counselling practices to become more evidence based. Although we support an evidentiary-based approach to the integration of genetic testing into practice, genetic advance is unlikely to occur in an orderly and standardized manner within countries, much less among different countries and health care systems4. Geneticists will become increasingly involved in professional education and policy-making regarding genetic testing and screening programs.

Motivators for participation in a whole-genome sequencing study: implications for translational genomics research.

The promise of personalized medicine depends on the ability to integrate genetic sequencing information into disease risk assessment for individuals. As genomic sequencing technology enters the realm of clinical care, its scale necessitates answers to key social and behavioral research questions about the complexities of understanding, communicating, and ultimately using sequence information to improve health. Our study captured the motivations and expectations of research participants who consented to participate in a research protocol, ClinSeq, which offers to return a subset of the data generated through high-throughput sequencing. We present findings from an exploratory study of 322 participants, most of whom identified themselves as white, non-Hispanic, and coming from higher socio-economic groups. Participants aged 45–65 years answered open-ended questions about the reasons they consented to ClinSeq and about what they anticipated would come of genomic sequencing. Two main reasons for participating were as follows: a conviction to altruism in promoting research, and a desire to learn more about genetic factors that contribute to ones own health risk. Overall, participants expected genomic research to help improve understanding of disease causes and treatments. Our findings offer a first glimpse into the motivations and expectations of individuals seeking their own genomic information, and provide initial insights into the value these early adopters of technology place on information generated by high-throughput sequencing studies.

Perceptions of genetic discrimination among at-risk relatives of colorectal cancer patients

Purpose: To explore the concerns of at-risk relatives of colorectal cancer patients about genetic discrimination and their awareness of current legislative protections.Methods: A questionnaire was sent to unaffected individuals with a family history of colorectal cancer who had enrolled in the Johns Hopkins Hereditary Colorectal Cancer Registry (N = 777).Results: Of the 470 respondents, approximately half rated their level of concern about genetic discrimination as high. The majority of respondents, 79%, learned about genetic discrimination from at least one media source (television, newspapers, magazines, and radio). If they were to pursue genetic testing, respondents with a higher level of concern about genetic discrimination would be significantly more likely to pay out of pocket, use an alias, or ask for test results to be excluded from their medical record. Awareness and understanding of legislation regarding genetic discrimination was found to be minimal.Conclusion: Findings from this study demonstrate the negative effect of concerns about genetic discrimination on decisions about utilization of genetic services. Stronger legislative protections against genetic discrimination and increased public education through the scientific community and media sources are needed.

Adaptation to living with a genetic condition or risk: a mini-review.

One goal of genetic counseling is to facilitate client adaptation to a genetic condition or risk. Adaptation refers to both the process of coming to terms with the implications of the condition or risk and the observable outcomes of that process. This review summarizes existing studies on how well clients adapt to living with a common chronic disease, and more specifically, a genetic condition. Overall, it appears that about one‐third of clients do not adjust well to the stress of living with a genetic condition or at risk. However, the data are limited by inconsistencies in the conceptualization of adaptation, a paucity of theoretical models, poor study design and inadequate outcome measures. Well‐designed studies based upon multidimensional models are needed that focus on familial as well as individual adaptation. We conclude with a summary of studies that have explored the use of interventions to enhance adaptation and suggest improved client outcomes. Further research should result in evidence‐based interventions to facilitate client adaptation that can be used effectively by genetic providers within the confines of their clinical work.

Turner Syndrome: Four Challenges Across the Lifespan

Turner syndrome (TS) is a sex chromosome condition that occurs in approximately 1/2,500 live female births. Despite the prevalence of this chromosomal condition, the challenges these women face throughout their lives are not fully understood. This qualitative research study aimed to characterize the subjective experiences of individuals with TS throughout their lifespan, to investigate their concerns and obstacles, and to offer insight into the strengths and weaknesses of health care delivery, as they perceived them. Ninety‐seven girls and women with TS and 21 parents consented to participate in this interview study. Interviews were semi‐structured and open‐ended in design. Questions sought to elicit responses relating to existing concerns associated with their condition and positive and negative health care experiences. Participants were divided into four age categories (childhood, adolescence, adulthood, and mature adulthood) to facilitate a comparative analysis across the age spectrum. Regardless of age, infertility was the most frequently cited concern followed closely by short stature. Sexual development and function and general health were also viewed as challenges by a number of participants in each age group. Although the relative weight of these four concerns tended to shift based upon the individuals age and life experiences, all four issues remained significant throughout the lifespan. Enhanced awareness of the evolving physical and psychological challenges faced by girls and women with TS may help health care providers (HCPs) improve the quality of life for these individuals. Published 2005 Wiley‐Liss, Inc.