There is consensus internationally that research participants should be offered the opportunity to receive clinically relevant genetic information identified through research, but there is little empirical peer-reviewed work documenting this process. We report the experience of conducting genetic research with nearly 35,000 participants in the Colon Cancer Family Registry, based in the USA, Canada, Australia, and New Zealand. Investigators from six multinational sites provided information about disclosure protocols, implementation, and uptake of genetic results and made suggestions to inform practice. Across 5 of the 6 registry sites, 1,634 participants in families with mismatch repair or MutYH gene mutations have been offered results. Participant uptake ranged from 56 to 86 %. Researchers faced significant challenges in the effort to return results. We offer suggestions in five key areas: (1) planning for the disclosure process, (2) participant information, (3) autonomy of participants, (4) monitoring scientific progress, and (5) involvement of stakeholders. Despite increasing discussion of the importance of returning incidental findings from genetic research, this paper highlights the considerable diversity, challenges, and costs faced in practice when returning expected findings with established utility and validity. We argue that more work is needed to ensure that genetic results in research are optimally managed.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Affleck P (2009) Is it ethical to deny genetic research participants individualised results? J Med Ethics 35(4):209–213. doi:10.1136/jme.2007.024034
Beskow LM, Burke W, Merz JF, Barr PA, Terry S, Penchaszadeh VB, Gostin LO, Gwinn M, Khoury MJ (2001) Informed consent for population-based research involving genetics. JAMA Am Med Assoc 286(18):2315–2321. doi:10.1001/jama.286.18.2315
Bookman E, Langehorne A, Eckfeldt J, Glass K, Jarvik G, Klag M, Koski G, Motulsky A, Wilfond B, Manolio T, Fabsitz R, Luepker R (2006) Reporting genetic results in research studies: summary and recommendations of an NHLBI working group. Am J Med Genet A 140A:1033–1040
Botkin JR, Teutsch SM, Kaye CI, Hayes M, Haddow JE, Bradley LA, Szegda K, Dotson WD, on behalf of the EWG (2010) Outcomes of interest in evidence-based evaluations of genetic tests. Genet Med 12(4):228–235
Ceballos R, Newcomb P, Beasley J, Petersen S, Templeton A, Hunt J (2008) Willingness to disclose genetic status to family members: a comparison of colon cancer cases and relatives. Genet Test Mol Biomark 12(3):415–420
Dressler LG (2009) Disclosure of research results from cancer genomic studies: state of the science. Clin Cancer Res 15(13):4270–4276. doi:10.1158/1078-0432.ccr-08-3067
Esplen M, Aronson M, Rothenmund H, Butler K, Gallinger S, Laceby J, Bapat B, Toner B, Wong J (2003) Motivation, anticipated distress and knowledge level of colorectal cancer patients undergoing genetic testing. Familial Cancer 1(70)
Esplen M, Aronson M, Rothenmund H, Butler K, Gallinger S (2004) Relatives of colorectal cancer patients participating in a population-based familial colorectal cancer registry. Psycho-Oncology 13(8)
Fabsitz R, McGuire A, Sharp R, Puggal M, Beskow L, Biesecker L, Bookman E, Burke W, Burchard E, Church G, Clayton E, Eckfeldt J, Fernandez C, Fisher R, Fullerton S, Gabriel S, Gachupin F, James C, Jarvik G, Kittles R, Leib J, O’Donnell C, O’Rourke P, Rodriguez L, Schully S, Shuldiner A, Sze R, Thakuria J, Wolf S, Burke G (2010) Ethical and practical guidelines for reporting genetic research results to study participants. Updated guidelines from a National Heart, Lung, and Blood Institute Working Group. Circ Cardiovasc Genet 3:574–580
Green RC, Berg JS, Berry GT, Biesecker LG, Dimmock DP, Evans JP, Grody WW, Hegde MR, Kalia S, Korf BR, Krantz I, McGuire AL, Miller DT, Murray MF, Nussbaum RL, Plon SE, Rehm HL, Jacob HJ (2012) Exploring concordance and discordance for return of incidental findings from clinical sequencing. Genet Med 14(4):405–410
Gritz E, Peterson S, Vernon S, Marani S, Baile W, Watts B, Amos C, Frazier M, Lynch P (2005) Psychological impact of genetic testing for hereditary nonpolyposis colorectal cancer. J Clin Oncol 23(9):1902–1910
Hutson S (2003) Attitudes and psychological impact of genetic testing, genetic counseling, and breast cancer risk assessment among women at increased risk. Oncol Nurs Forum 30(2):241–246
Järvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P, De La Chapelle A, Mecklin JP (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118(5):829–834
Kaufman D, Murphy J, Scott J, Hudson K (2008) Subjects matter: a survey of public opinions about a large genetic cohort study. Genet Med 10(11):813–839
Keogh L, van Vliet C, Studdert D, Maskiell J, McCrae F, John DS, Gaff C, Young M, Southey M, Giles G, Rosenthal D, Hopper J, Jenkins M (2009) Is uptake of genetic testing for colorectal cancer influenced by implications for insurance? Med J Aust 191(5):255–258
Knoppers B, Joly Y, Simard J, Durocher F (2006) The emergence of an ethical duty to disclose genetic research results: international perspectives. Eur J Med Genet 14(12):1322
Kollek R, Petersen I (2011) Disclosure of individual research results in clinico-genomic trials: challenges, classification and criteria for decision-making. J Med Ethics 37:271–275
Lindor N, Sloan J, Goldberg R, Bowen D, Nigon S, Roche A, Petersen G, Thibodeau S, Burgart L, Leontovich O, Morlan B (2004) Colorectal tumour microsatellite instability test results: perspectives from patients. Hereditary Cancer Clin Pract 2(2):69–75
Lindor N, Robe K, Petersen G, Haile R, Casey G, Baron J, Bapat B, Aranson M, Hopper J, Jass J, Le Marchand L, Grove J, Potter J, Newcomb P, Terdiman J, Conrad P, Moslein G, Goldberg R, Ziogas A, Anton-Culver H, de Andrade M, Siegmund K, Thibodeau S, Boardman L, Seminara D (2005) Lower cancer incidence in Amsterdam-I Criteria families without mismatch repair deficiency. Familial Colorectal Cancer Type X. J Am Med Assoc 293(16):1979–1985
Meiser B (2005) Psychological impact of genetic testing for cancer susceptibility: an update of the literature. Psychoonology 14(12):1060–1064
Meulenkamp T, Gevers S, Bovenberg J, Koppelman G, van Hylckama VA, Smets E (2010) Communication of biobanks’ research results: what do (potential) participants want? Am J Med Genet 152A(10):2482–2492
Miller FA, Christensen R, Giacomini M, Robert JS (2008) Duty to disclose what? Querying the putative obligation to return research results to participants. J Med Ethics 34(3):210–213. doi:10.1136/jme.2006.020289
National Health and Medical Research Council (2007) National statement on ethical conduct in human research. Available at http://www.nhmrc.gov.au/publications/synopses/e72syn.htm
Newcomb P, Baron J, Cotterchio M, Gallinger S, Grove J, Haile R, Hall D, Hopper J, Jass J, Le Marchand L, Limburg P, Lindor N, Potter J, Templeton A, Thibodeau A, Seminara D (2007) Colon Cancer Family Registry: an international resource for studies of the genetic epidemiology of colon cancer. Cancer Epidemiol Biomark Prev 16(11):2331–2343
Palomaki GE, McClain MR, Melillo S, Hampel HL, Thibodeau SN (2009) EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med 11(1):42–65
Partridge AH, Winer EP (2002) Informing clinical trial participants about study results. JAMA J Am Med Assoc 288(3):363–365. doi:10.1001/jama.288.3.363
Ravitsky V, Wilfond B (2006) Disclosing individual genetic results to research participants. Am J Bioeth 6(6):8–17
Roberts J, Shalowitz D, Christnesen K, Everett J, Kim S, Raskin L, Gruber S (2010) Returning individual results: development of a cancer genetics education and risk communication protocol. J Empir Res Hum Res Ethics 15(3):17–30
Rothstein M (2006) Tiered disclosure options promote the autonomy and well-being of research subjects. Am J Bioeth 6(6):20–21
Schully SD, Benedicto CB, Gillanders EM, Wang SS, Khoury MJ (2011) Translational research in cancer genetics: the road less traveled. Public Health Genomics 14(1):1–8
Terdiman JP (2009) MYH-associated disease: attenuated adenomatous polyposis of the colon is only part of the story. Gastroenterology 137(6):1883–1886
Theodoratou E, Campbell H, Tenesa A, Houlston R, Webb E, Lubbe S, Broderick P, Gallinger S, Croitoru EM, Jenkins MA, Win AK, Cleary SP, Koessler T, Pharoah PD, Kury S, Bezieau S, Buecher B, Ellis NA, Peterlongo P, Offit K, Aaltonen LA, Enholm S, Lindblom A, Zhou XL, Tomlinson IP, Moreno V, Blanco I, Capella G, Barnetson R, Porteous ME, Dunlop MG, Farrington SM (2010) A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants. Br J Cancer 103(12):1875–1884
Vasen HFA, Mecklin JP, Meera Khan P, Lynch HT (1991) The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 34(5):424–425
Wolf S, Paradise J, Caga-anan C (2008) The law of incidental findings in human subjects research: establishing researcher’s duties. J Law Med Ethics 36(2):361–383, 214
Wolf SM, Crock BN, Van Ness B, Lawrenz F, Kahn JP, Beskow LM, Cho MK, Christman MF, Green RC, Hall R, Illes J, Keane M, Knoppers BM, Koenig BA, Kohane IS, LeRoy B, Maschke KJ, McGeveran W, Ossorio P, Parker LS, Petersen GM, Richardson HS, Scott JA, Terry SF, Wilfond BS, Wolf WA (2012) Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genet Med 14(4):361–384
Zierhut H, Austin J (2011) How inclusion of genetic counselors on the research team can benefit translational science. Sci Transl Med 3(74):1–3. doi:10.1126/scitranslmed.3001898
This work was supported by the National Cancer Institute, National Institutes of Health under RFA-CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and PIs. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CFR. We acknowledge each of the sites of the Colon CFR for contributing their experiences and data to this study: Australasian Colorectal Cancer Family Registry (U01 CA097735), Familial Colorectal Neoplasia Collaborative Group (U01 CA074799) [USC], Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794), University of Hawaii Colorectal Cancer Family Registry (U01 CA074806), and University of California, Irvine Informatics Center (U01 CA078296). We thank the members of the Translation Working Group who contributed to the ongoing discussion about disclosure of research and to the development of our recommendations. We also acknowledge the participants in each of the Colon Cancer Family Registries for their contribution. All authors of this manuscript have participated in its drafting and have read and approved the final version submitted.
Conflict of interest
There are no conflicts of interest.
About this article
Cite this article
Keogh, L.A., Fisher, D., Sheinfeld Gorin, S. et al. How do researchers manage genetic results in practice? The experience of the multinational Colon Cancer Family Registry. J Community Genet 5, 99–108 (2014). https://doi.org/10.1007/s12687-013-0148-y