Returning genetic research panel results for breast cancer susceptibility

描述（由申请人提供）：癌症易感性的基因筛查（如BRCA1/2）已成为癌症预防的标准循证实践，并已被证明可以降低乳腺癌的发病率和死亡率。然而，大多数怀疑遗传易感性的个人和家庭并没有BRCA1/2突变。采用下一代测序技术的研究表明，PALB2、CHEK2和ATM等其他基因的突变与乳腺癌风险升高有关。因此，已经开发出多重面板，以有效地同时筛选大量基因，包括不同外显率和癌症谱的基因，并对知情同意和遗传咨询提出了挑战。尽管这些基因中的许多没有明确的临床应用证据，但这些基因面板现在已经可以在商业上获得并越来越多地使用。随着使用DNA库进行的大型前瞻性队列研究越来越多地用于评估基因、环境和生活方式的影响，人们一直在争论是否有义务与研究参与者分享个人研究结果（IRR）。作为多路面板

DESCRIPTION (provided by applicant): Genetic screening for cancer susceptibility (e.g. BRCA1/2) has become a standard evidence-based practice in cancer prevention and has proven to reduce breast cancer morbidity and mortality. Yet, most individuals and families in whom genetic susceptibility is suspected do not have a BRCA1/2 mutation. Research employing next generation sequencing has revealed that mutations in other genes, such as PALB2, CHEK2 and ATM are associated with elevated risks of breast cancer. Thus, multiplex panels have been developed to efficiently screen a large number of genes simultaneously, including genes of varied penetrance and cancer spectrum and presenting challenges to informed consent and genetic counseling. Despite no clear evidence of clinical utility for many of these genes, these gene panels are now commercially available and increasingly utilized. As large prospective cohort studies with banked DNA have become increasingly utilized to evaluate the effects of genes, the environment and lifestyle, there has been debate over the obligations, if any, to share individual research results (IRR) with research participants. As multiplex panels for breast cancer susceptibility illustrate, some genetic research findings will be associated with health outcomes and/or become available for clinical testing. Yet, there is no consensus on if, how, when and what information should be returned to research participants as these tests become clinically available. Further, the associated costs of returning IRR are unknown, and who should bear the costs of these activities has not been resolved. The overall goal of the proposed longitudinal multi-center study is to evaluate the risks, benefits, utilities and costs of returning multiplex genetic research results for breast cancer susceptibility to geographically and sociodemographically diverse research populations. Our theoretical model grounded in the Self- Regulation Theory of Health Behavior was developed to inform the selection of the short-term and longitudinal outcomes and potential mediators and moderators of these outcomes to inform the debate over risks, benefits and utility of returning IRR. Additionally, we include a broadened conceptualization of the "actual" utility of genomic test results. In Aim 1, we will evaluate uptake of IRR among research participants (Aim 1a), and factors associated with uptake (Aim 1b). In Aim 2, we will evaluate the short-term (Aim 2a) and longitudinal (Aim 2b) risks and benefits (i.e. patients understanding, reactions to, use and perceived utility of genomic information) of returning multiplex genetic research results. We will also evaluate the moderators of these outcomes (e.g. subgroups for whom the return of IRR is more or less beneficial). Equally important we will examine the short-term and longitudinal participant costs, research team costs and medical care utilization and costs with return or IRR (Aim 3a) and moderators of these costs (Aim 3b). We expect this research to inform the ongoing debate and ultimately evidence based guidelines for return of individual genomic research results.