Germline mutations in BRCA1 and BRCA2 incidentally revealed in a biobank research study: experiences from re-contacting mutation carriers and relatives

Martin P Nilsson, Monica Emmertz, Ulf Kristoffersson, Åke Borg, Christer Larsson, Martin Rehn, Christof Winter, Lao H Saal, Yvonne Brandberg, Niklas Loman, Martin P Nilsson, Monica Emmertz, Ulf Kristoffersson, Åke Borg, Christer Larsson, Martin Rehn, Christof Winter, Lao H Saal, Yvonne Brandberg, Niklas Loman

Abstract

Once an incidental finding (IF) is discovered in the course of genomic research, the researchers are faced with the question of whether or not that finding should be reported back to the study participant. A large number of hypothetical studies and policy documents on this issue have been published, but there are very few empirical studies to inform the bioethics debate. Within a biobank research study of somatic mutations in breast carcinomas, ten germline BRCA1/2 mutations were incidentally detected. After thorough discussions within a group of experts, the mutation carriers (n = 7) or relatives of deceased carriers (n = 3) were re-contacted and informed about the findings. Eight out of ten accepted to receive the information and underwent confirmatory testing. One year later, semi-structured interviews were undertaken with three of the study participants. All of them felt that BRCA mutations discovered in the course of research should be reported back to the individual study participants. In this paper, we report our step-by-step experiences of the re-contacting process. We hope that our detailed reporting will be helpful for other researchers and clinicians that are faced with similar situations. The results of our study lend empirical support to opinion that IFs that meet the three baseline criteria of analytic validity, clinical significance, and actionability should be reported back to the individual study participants.

Keywords: BRCA1; BRCA2; Biobank; Genetic; Incidental findings.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest

References

    1. Catenacci DV, Amico AL, Nielsen SM, Geynisman DM, Rambo B, Carey GB, Gulden C, Fackenthal J, Marsh RD, Kindler HL, Olopade OI. Tumor genome analysis includes germline genome: are we ready for surprises? Int J Cancer. 2015;136(7):1559–1567. doi: 10.1002/ijc.29128.
    1. Fleming J, Critchley C, Otlowski M, Stewart C, Kerridge I. Attitudes of the general public towards the disclosure of individual research results and incidental findings from biobank genomic research in Australia. Intern Med J. 2015;45(12):1274–1279. doi: 10.1111/imj.12911.
    1. Gliwa C, Yurkiewicz IR, Lehmann LS, Hull SC, Jones N, Berkman BE. Institutional review board perspectives on obligations to disclose genetic incidental findings to research participants. Genet Med. 2016;18(7):705–711. doi: 10.1038/gim.2015.149.
    1. Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013;15(7):565–574. doi: 10.1038/gim.2013.73.
    1. Hallowell N, Alsop K, Gleeson M, Crook A, Plunkett L, Bowtell D, Mitchell G, Young MA. The responses of research participants and their next of kin to receiving feedback of genetic test results following participation in the Australian Ovarian Cancer Study. Genet Med. 2013;15(6):458–465. doi: 10.1038/gim.2012.154.
    1. Haukkala A, Kujala E, Alha P, Salomaa V, Koskinen S, Swan H, Kaariainen H. The return of unexpected research results in a biobank study and referral to health care for heritable long QT syndrome. Public Health Genomics. 2013;16(5):241–250. doi: 10.1159/000354105.
    1. Hehir-Kwa JY, Claustres M, Hastings RJ, van Ravenswaaij-Arts C, Christenhusz G, Genuardi M, Melegh B, Cambon-Thomsen A, Patsalis P, Vermeesch J, Cornel MC, Searle B, Palotie A, Capoluongo E, Peterlin B, Estivill X, Robinson PN. Towards a European consensus for reporting incidental findings during clinical NGS testing. Eur J Human Genet. 2015;23(12):1601–1606. doi: 10.1038/ejhg.2015.111.
    1. Jelsig AM, Qvist N, Brusgaard K, Ousager LB. Research participants in NGS studies want to know about incidental findings. Eur J Human Genet. 2015;23(10):1423–1426. doi: 10.1038/ejhg.2014.298.
    1. JH Y, Harrell TM, Jamal SM, Tabor HK, Bamshad MJ. Attitudes of genetics professionals toward the return of incidental results from exome and whole-genome sequencing. Am J Hum Genet. 2014;95(1):77–84. doi: 10.1016/j.ajhg.2014.06.004.
    1. Keogh LA, Southey MC, Maskiell J, Young MA, Gaff CL, Kirk J, Tucker KM, Rosenthal D, McCredie MR, Giles GG, Hopper JL. Uptake of offer to receive genetic information about BRCA1 and BRCA2 mutations in an Australian population-based study. Cancer Epidemiol Biomarkers Prev. 2004;13(12):2258–2263.
    1. Knoppers BM, Zawati MH, Senecal K. Return of genetic testing results in the era of whole-genome sequencing. Nat Rev Genet. 2015;16(9):553–559. doi: 10.1038/nrg3960.
    1. Meulenkamp TM, Gevers SK, Bovenberg JA, Koppelman GH, van Hylckama Vlieg A, Smets EM. Communication of biobanks’ research results: what do (potential) participants want? Am J Med Genet A. 2010;152A(10):2482–2492. doi: 10.1002/ajmg.a.33617.
    1. Nilsson MP, Winter C, Kristoffersson U, Rehn M, Larsson C, Saal LH, Loman N. Efficacy versus effectiveness of clinical genetic testing criteria for BRCA1 and BRCA2 hereditary mutations in incident breast cancer. Familial Cancer. 2017;16(2):187–193. doi: 10.1007/s10689-016-9953-x.
    1. Ormondroyd E, Moynihan C, Watson M, Foster C, Davolls S, Ardern-Jones A, Eeles R. Disclosure of genetics research results after the death of the patient participant: a qualitative study of the impact on relatives. J Genet Couns. 2007;16(4):527–538. doi: 10.1007/s10897-007-9088-1.
    1. Pulford DJ, Harter P, Floquet A, Barrett C, Suh DH, Friedlander M, Arranz JA, Hasegawa K, Tada H, Vuylsteke P, Mirza MR, Donadello N, Scambia G, Johnson T, Cox C, Chan JK, Imhof M, Herzog TJ, Calvert P, Wimberger P, Berton-Rigaud D, Lim MC, Elser G, CF X, du Bois A. Communicating BRCA research results to patients enrolled in international clinical trials: lessons learnt from the AGO-OVAR 16 study. BMC Medical Ethics. 2016;17(1):63. doi: 10.1186/s12910-016-0144-y.
    1. Richards MP, Ponder M, Pharoah P, Everest S, Mackay J. Issues of consent and feedback in a genetic epidemiological study of women with breast cancer. J Med Ethics. 2003;29(2):93–96. doi: 10.1136/jme.29.2.93.
    1. Shkedi-Rafid S, Dheensa S, Crawford G, Fenwick A, Lucassen A. Defining and managing incidental findings in genetic and genomic practice. J Med Genet. 2014;51(11):715–723. doi: 10.1136/jmedgenet-2014-102435.
    1. Viberg J, Hansson MG, Langenskiold S, Segerdahl P. Incidental findings: the time is not yet ripe for a policy for biobanks. Eur J Human Genet. 2014;22(4):437–441. doi: 10.1038/ejhg.2013.217.
    1. Viberg J, Segerdahl P, Langenskiold S, Hansson MG. Freedom of choice about incidental findings can frustrate participants’ true preferences. Bioethics. 2016;30(3):203–209. doi: 10.1111/bioe.12160.
    1. Winter C, Nilsson MP, Olsson E, George AM, Chen Y, Kvist A, Torngren T, Vallon-Christersson J, Hegardt C, Hakkinen J, Jonsson G, Grabau D, Malmberg M, Kristoffersson U, Rehn M, Gruvberger-Saal SK, Larsson C, Borg A, Loman N, Saal LH. Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic. Ann Oncol. 2016;27(8):1532–1538. doi: 10.1093/annonc/mdw209.
    1. Wolf SM, Lawrenz FP, Nelson CA, Kahn JP, Cho MK, Clayton EW, Fletcher JG, Georgieff MK, Hammerschmidt D, Hudson K, Illes J, Kapur V, Keane MA, Koenig BA, Leroy BS, McFarland EG, Paradise J, Parker LS, Terry SF, Van Ness B, Wilfond BS. Managing incidental findings in human subjects research: analysis and recommendations. J Law Med Ethics. 2008;36(2):219–248. doi: 10.1111/j.1748-720X.2008.00266.x.

Source: PubMed

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