Disclosing genomic incidental findings in a cancer biobank: An ELSI experiment

This empirical bioethics research project will inform policy debates about the disclosure of genomic incidental findings (GIFD), a much disputed topic. We will conduct an experiment designed to develop effective ethical strategies for offering genomic incidental findings to participants in a biobank for pancreatic cancer. Our approach will be informed by studying the preferences of biobank research participants (and family members) using mixed methods; to our knowledge, no previous research has addressed this topic. Mayo Clinic investigators, led by PI Gloria Petersen, have collected germline DNA of pancreatic cancer probands in a biobank created for gene discovery. While seeking novel pancreatic cancer variants, we have identified 76 probands who are germline carriers of mutations in genes that are 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 often disclosed in clinical practice and have health implications, we will offer GIFD.

However, given that the majority of biobank probands are deceased, many practical concerns arise, as well as ethical, legal, and social considerations that require further study:

  • Who should be informed, 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?
  • Should aggregate or individual results be offered?
  • What disclosure procedures best meet family members’ concerns?
  • Should family members be informed individually or as a group?
  • Is there an ethical threshold for determining when the researcher is obligated to offer GIFD?

This ELSI experiment leverages the infrastructure of an NCI-funded SPORE cancer biobank and addresses an immediate problem in translational genomics research ethics. A partnership between the two PIs (a genetic epidemiologist and an empirical bioethics scholar) enables immediate access to a sample of 2,400 individuals (probands, family members, and next of kin). The Specific Aims—which combine descriptive and normative objectives— are:

  1.  To assess a priori preferences of pancreatic cancer probands and family members about whether they desire and expect to receive genetic results that carry health risks not related to pancreatic cancer (using interviews and a survey) 
  2. Based on the findings from Aim 1, and deliberation by the investigators, patient advocates, and ELSI scholars, to develop, prototype, and evaluate novel procedures for offering genetic results to family members of probands who tested positive for the three mutations
  3. To develop “best practice” guidelines and recommendations for offering GIFD to family members of biobank participants, including refinements to the biobank informed consent process and creation of practice guidelines that will inform genomic biobank governance.