Fisher, Douglass

3567 Background: The ability to genotype large numbers of people rapidly and inexpensively for research purposes highlights the need to develop guidelines for providing medically-relevant research results - including unanticipated findings - to study participants. The Colon Cancer Family Registry (C-CFR) is the oldest and largest international colon cancer population-based registry; its experience managing genetic research findings can offer guidance to clinicians and researchers. The C-CFR has enrolled 10,019 cases with colon cancer and 24,708 family members in six registries in the US, Canada, Australia, and New Zealand. Deleterious (“high risk”) germline mutations have been identified in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) and the MutYH gene. The aims of this presentation are to: (1) report the uptake of genetic test results by C-CFR participants; (2) systematically compare disclosure protocols and barriers to uptake by registry; (3) make recommendations to guide clinicians and researchers. Methods: Uptake of genetic test results was calculated from data collected by the C-CFR; key investigators (KIs) from each registry completed a survey about disclosure decision-making; KIs also took part in discussions to generate recommendations. Results: Registry-wide molecular testing has identified deleterious MMR germline mutations for at least one member of 424 families (4%) and 48 biallelic MutYH gene carriers. Uptake of test results ranged from 56-86% (n= 1542) across registries. Barriers to disclosure include: (1) lack of pre-existing notification protocols; (2) logistics of re-consent; (3) limited involvement of genetic counselors at some registries; (4) in the US, the requirement that genetic testing be performed in a CLIA approved laboratory; (5) IRBs declining approval; and (6) budget constraints. Conclusions: Based on our international registry’s findings we recommend that researchers generating genetic information establish plans for disclosure at the outset; obtain subject consent a priori; consider subject knowledge and disclosure preferences; provide guidance and budget for clinical follow-up; and involve genetic counselors.

AbstractBackgroundThe extent to which participants act to clinically verify research results is largely unknown. This study examined whether participants who received Lynch syndrome (LS)‐related findings pursued researchers’ recommendation to clinically verify results with testing performed by a CLIA‐certified laboratory.MethodsThe Fred Hutchinson Cancer Research Center site of the multinational Colon Cancer Family Registry offered non‐CLIA individual genetic research results to select registry participants (cases and their enrolled relatives) from 2011 to 2013. Participants who elected to receive results were counseled on the importance of verifying results at a CLIA‐certified laboratory. Twenty‐six (76.5%) of the 34 participants who received genetic results completed 2‐ and 12‐month postdisclosure surveys; 42.3% of these (11/26) participated in a semistructured follow‐up interview.ResultsWithin 12 months of result disclosure, only 4 (15.4%) of 26 participants reported having verified their results in a CLIA‐certified laboratory; of these four cases, all research and clinical results were concordant. Reasons for pursuing clinical verification included acting on the recommendation of the research team and informing future clinical care. Those who did not verify results cited lack of insurance coverage and limited perceived personal benefit of clinical verification as reasons for inaction.ConclusionThese findings suggest researchers will need to address barriers to seeking clinical verification in order to ensure that the intended benefits of returning genetic research results are realized.