Disclosing Genomic Incidental Findings in a Cancer Biobank: An ELSI Experiment

描述（由申请人提供）：这个实证和规范的生物伦理学研究项目将指导关于基因组偶然发现（GIFD）披露的政策和实践，这是一个备受争议的话题。在多学科ELSI工作组的伦理指导下，我们将进行一项实验，旨在制定将偶然发现提供给胰腺癌生物库中先显子家庭成员的策略。我们的方法将通过研究生物库研究参与者（包括亲属）的偏好来获得信息。据我们所知，以前没有研究涉及到将偶然发现归还给家庭。然而，生物银行面临着这个问题。迫切需要指导实践的建议。梅奥诊所在nci资助的SPORE生物库中收集了胰腺癌先证者的种系DNA，该生物库是为基因发现而创建的。在寻找新的胰腺癌变异时，我们已经确定了73个先证，他们是已知会增加胰腺癌以外疾病风险的基因突变的种系携带者：BRCA2（乳腺癌和卵巢癌），CDKN2A/p16（恶性黑色素瘤）和CFTR（后代囊性纤维化）。由于这些突变在临床实践中经常被披露，并且具有严重的健康和/或生殖影响，因此考虑GIFD是合理的。考虑到大多数胰腺癌先证者已经去世，许多问题出现了：如果先证者的法定近亲被告知可能无法确保生物学上有风险的家庭成员被告知，那么谁应该被告知这些发现？由于亲属没有参与最初的生物库知情同意过程，如何管理重新联系？什么样的披露程序最能满足家庭成员的关切？是否有道德门槛来决定研究者何时有义务提供GIFD？3位pisi的合作伙伴——指导孢子生物银行的遗传流行病学家格洛丽亚·彼得森（Gloria Petersen），经验研究员芭芭拉·柯尼格（Barbara Koenig），生物伦理学和法律学者苏珊·沃尔夫（Susan Wolf）——结合了梅奥诊所和明尼苏达大学（UMN）的优势。该项目利用了梅奥诊所孢子生物银行的基础设施和UMN的法律和价值观联盟对nhgri资助的偶然发现工作的历史。该项目解决了翻译基因组学研究伦理中的一个关键问题。具体目标-结合描述性和规范性目标-是：(1)通过a)访谈和b)调查来评估胰腺癌先证者及其家庭成员的偏好；(2)与法律和生命伦理专家工作组进行深入的ELSI分析，形成共识性建议；(3)基于目标1和目标2的发现，原型化并评估一种向携带生殖系突变的先证者的家庭成员提供发现的程序；(4)制定“最佳实践”指南。该项目将收集有关先证地和家庭偏好的急需数据，对所提出的法律和伦理问题进行详细分析，形成共识建议，制定尊重偏好的方法，并推进健全的生物样本库治理。

DESCRIPTION (provided by applicant): This empirical and normative bioethics research project will guide policy and practice about the disclosure of genomic incidental findings (GIFD), a much-debated topic. With ethical guidance from a multidisciplinary ELSI Working Group, we will conduct an experiment designed to develop strategies for offering incidental findings to family members of probands in a biobank for pancreatic cancer. Our approach will be informed by studying the preferences of biobank research participants (including kin).To our knowledge, no previous research has addressed the return of incidental findings to families. Yet biobanks face this question. Recommendations to guide practice are sorely needed. Mayo Clinic has collected germline DNA of pancreatic cancer probands in an NCI-funded SPORE biobank created for gene discovery. While seeking novel pancreatic cancer variants, we have identified 73 probands who are germline carriers of mutations in genes known to confer increased risk of diseases other than pancreatic cancer: BRCA2 (breast & ovarian cancer), CDKN2A/p16 (malignant melanoma), and CFTR (cystic fibrosis in offspring). Because these mutations are routinely disclosed in clinical practice and have serious health and/or reproductive implications, consideration of GIFD is justified. Given that the majority of the pancreatic cancer probands are deceased, many concerns arise: Who should be offered the findings, given that notification of the proband's legal next of kin may not assure that biologically at-risk family members are informed? Since relatives were not involved in the original biobank informed consent process, how should re-contact be managed? What disclosure proce- dures best meet family members' concerns? Is there an ethical threshold for determining when the researcher is obligated to offer GIFD? A partnership among 3 PIs-a genetic epidemiologist who directs the SPORE biobank (Gloria Petersen), an empirical researcher (Barbara Koenig), and a bioethics and law scholar (Susan Wolf)-combines the strengths of Mayo Clinic and the University of Minnesota (UMN). This project leverages the infrastructure of the SPORE biobank at Mayo Clinic and UMN's Consortium on Law and Values' history of NHGRI-funded work on incidental findings. This project addresses a critical problem in translational genomics research ethics. The Specific Aims-which combine descriptive and normative objectives-are: (1) to assess preferences of pancreatic cancer probands and their family members using a) interviews and b) a survey; (2) to conduct an in-depth ELSI analysis with an expert law and bioethics Working Group, leading to consensus recommendations; (3) based on the findings from Aims 1 and 2, to prototype and evaluate a procedure for offering findings to family members of probands who carry germline mutations; and (4) to develop "best practice" guidelines. This project will generate much-needed data on proband and family preferences, produce detailed analyses of the legal and ethical issues raised, create consensus recommendations, devise methods for honoring preferences, and advance sound biobank governance.