Skip to main content
SpringerLink
Log in

Timing and context: important considerations in the return of genetic results to research participants

  • Original Article
  • Published:
Journal of Community Genetics Aims and scope Submit manuscript

Abstract

General consensus exists that clinically significant germline genetic research results should be fed back to research participants. A body of literature is emerging about Australian research participants’ experiences of feedback of genetic research results and factors that influence a participant’s actions after receiving such information. This exploratory qualitative study conducted interviews with 11 participants from the International Sarcoma Kindred Study, four probands and seven of their relatives. They had been informed by letter of the availability of clinically significant germline TP53 mutations identified through research. We examined the participants’ views about the feedback of these genetic test results. Thematic (inductive) analysis was used to analyse the data. A number of factors influenced participants’ responses following notification. This included participants’ understanding of the notification letter and their perception of the relevance of the information for them and/or their family. Most notably, timing of the letter in the context of an individual’s current life experiences was important. Timing and context are novel factors identified that may impact on research participants’ understanding or their ability to access clinically significant research results. We outline strategies for disseminating results to research participants and their next of kin that may reduce their uncertainty around the receipt of research results.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Barlow-Stewart K, Taylor SD, Treloar SA, Stranger M, Otlowski M (2009) Verification of consumers’ experiences and perceptions of genetic discrimination and its impact on utilization of genetic testing. Genet Med 11(3):193–201. doi:10.1097/GIM.0b013e318194ee75

    Article  PubMed  Google Scholar 

  • Biesecker BB, Ishibe N, Hadley DW, Giambarresi TR, Kase RG, Lerman C, Struewing JP (2000) Psychosocial factors predicting BRCA1/BRCA2 testing decisions in members of hereditary breast and ovarian cancer families. Am J Med Genet 93(4):257–263. doi:10.1002/1096-8628(20000814)93:4<257::aid-ajmg1>3.0.co;2-8

    Article  PubMed  CAS  Google Scholar 

  • Birch JM, Alston RD, McNally RJQ, Evans DGR, Kelsey AM, Harris M, Eden OB, Varley JM (2001) Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20(34):4621–4628. doi:10.1038/sj.onc.1204621

    Article  PubMed  CAS  Google Scholar 

  • Bishop DT, Demenais F, Goldstein AM, Bergman W, Bishop JN, Bressac-de Paillerets B, Chompret A, Ghiorzo P, Gruis N, Hansson J, Harland M, Hayward N, Holland EA, Mann GJ, Mantelli M, Nancarrow D, Platz A, Tucker MA, Melanoma Genetics C (2002) Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst 94(12):894–903

    Article  PubMed  CAS  Google Scholar 

  • Bollinger J, Scott J, Dvoskin R, Kaufman D (2012) Public preferences regarding the return of individual genetic research results: findings from a qualitative focus group study. Genet Med 14(4):451–457

    Article  PubMed  PubMed Central  Google Scholar 

  • Botkin JR, Smith KR, Croyle RT, Baty BJ, Wylie JE, Dutson D, Chan A, Hamann HA, Lerman C, McDonald J, Venne V, Ward JH, Lyon E (2003) Genetic testing for a BRCA1 mutation: prophylactic surgery and screening behavior in women 2 years post testing. Am J Med Genet A 118A(3):201–209. doi:10.1002/ajmg.a.10102

    Article  PubMed  Google Scholar 

  • Bredenoord AL, Kroes HY, Cuppen E, Parker M, van Delden JJM (2011a) Disclosure of individual genetic data to research participants: the debate reconsidered. Trends Genet 27(2):41–47. doi:10.1016/j.tig.2010.11.004

    Article  PubMed  CAS  Google Scholar 

  • Bredenoord AL, Onland-Moret NC, Van Delden JJM (2011b) Feedback of individual genetic results to research participants: in favor of a qualified disclosure policy. Hum Mutat 32(8):861–867. doi:10.1002/humu.21518

    Article  PubMed  Google Scholar 

  • Christensen KD, Roberts JS, Shalowitz DI, Everett JN, Kim SYH, Raskin L, Gruber SB (2011) Disclosing individual CDKN2A research results to melanoma survivors: interest, impact, and demands on researchers. Cancer Epidemiol Biomark Prev 20(3):522–529. doi:10.1158/1055-9965.epi-10-1045

    Article  CAS  Google Scholar 

  • Clayton EW (2008) Incidental findings in genetics research using archived DNA. J Law Med Ethics 36(2):286. doi:10.1111/j.1748-720X.2008.00271.x

    Article  PubMed  PubMed Central  Google Scholar 

  • Crook A, Plunkett L, Forrest L, Hallowell N, Alsop SW, Gleeson M, Bowtell D, Mitchell G, Group TAOCS, Young M (2014) Connecting patients, researchers and clinical genetics services: the experiences of participants in the Australian Ovarian Cancer Study (AOCS). Eur J Hum Genet. doi:10.1038/ejhg.2014.86

    PubMed  Google Scholar 

  • Dancyger C, Smith JA, Jacobs C, Wallace M, Michie S (2010) Comparing family members’ motivations and attitudes towards genetic testing for hereditary breast and ovarian cancer: a qualitative analysis. Eur J Hum Genet 18(12):1289–1295. doi:10.1038/ejhg.2010.114

    Article  PubMed  PubMed Central  Google Scholar 

  • Etchegary H, Miller F, Delaat S, Wilson B, Carroll J, Cappelli M (2009) Decision-making about inherited cancer risk: exploring dimensions of genetic responsibility. J Genet Couns 18(3):252–264. doi:10.1007/s10897-009-9218-z

    Article  PubMed  Google Scholar 

  • Fernandez C (2008) Public expectations for return of results time to stop being paternalistic? AmJ Bioeth 8(11):46–48. doi:10.1080/15265160802513127

    Article  Google Scholar 

  • Garber JE, Goldstein AM, Kantor AF, Dreyfus MG, Fraumeni JF, Li FP (1991) Follow up study of 24 families with Li-Fraumeni syndrome. Cancer Res 51(22):6094–6097

    PubMed  CAS  Google Scholar 

  • Geer KP, Ropka ME, Cohn WF, Jones SM, Miesfeldt S (2001) Factors influencing patients’ decisions to decline cancer genetic counseling services. J Genet Couns 10(1):25–40. doi:10.1023/a:1009451213035

    Article  PubMed  CAS  Google Scholar 

  • Gerdes M, Terry SF (2014) Five principles: returning genetic testing results to research participants. Genet Test Mol Biomark 18(7):453–454. doi:10.1089/gtmb.2014.1556

    Article  Google Scholar 

  • Godard B, Pratte A, Dumont M, Simard-Lebrun A, Simard J (2007) Factors associated with an individual’s decision to withdraw from genetic testing for breast and ovarian cancer susceptibility: implications for counseling. Genet Test 11(1):45–54. doi:10.1089/gte.2006.9998

    Article  PubMed  Google Scholar 

  • Hallowell N (1999) Doing the right thing: genetic risk and responsibility. Sociol Health Illn 21(5):597–621. doi:10.1111/1467-9566.00175

    Article  Google Scholar 

  • Hallowell N, Foster C, Eeles R, Ardern-Jones A, Murday V, Watson M (2003) Balancing autonomy and responsibility: the ethics of generating and disclosing genetic information. J Med Ethics 29(2):74–79. doi:10.1136/jme.29.2.74

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hallowell N, Alsop K, Gleeson M, Crook A, Plunkett L, Bowtell D, Mitchell G, Young M-A, Australian Ovarian Canc Study G (2013) 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 15(6):458–465. doi:10.1038/gim.2012.154

    Article  PubMed  CAS  Google Scholar 

  • Hayward NK (2003) Genetics of melanoma predisposition. Oncogene 22(20):3053–3062. doi:10.1038/sj.onc.1206445

    Article  PubMed  CAS  Google Scholar 

  • Heymann S, Delaloge S, Rahal A, Caron O, Frebourg T, Barreau L, Pachet C, Mathieu M-C, Marsiglia H, Bourgier C (2010) Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome. Radiat Oncol 5:104. doi:10.1186/1748-717x-5-104

    Article  PubMed  PubMed Central  Google Scholar 

  • Hisada M, Garber JE, Fung CY, Fraumeni JF, Li FP (1998) Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90(8):606–611

    Article  PubMed  CAS  Google Scholar 

  • Hwang SJ, Lozano G, Amos CI, Strong LC (2003) Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk. Am J Hum Genet 72(4):975–983

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kasparian NA, Meiser B, Butow PN, Job RFS, Mann GJ (2006) Better the devil you know? High-risk individuals' anticipated psychological responses to genetic testing for melanoma susceptibility. J Genet Couns 15(6):433–447. doi:10.1007/s10897-006-9038-3

    Article  PubMed  Google Scholar 

  • Kasparian NA, Meiser B, Butow PN, Simpson JM, Mann GJ (2009) Genetic testing for melanoma risk: a prospective cohort study of uptake and outcomes among Australian families. Genet Med 11(4):265–278. doi:10.1097/GIM.0b013e3181993175

    Article  PubMed  Google Scholar 

  • Kaye J, Curren L, Anderson N, Edwards K, Fullerton SM, Kanellopoulou N, Lund D, MacArthur DG, Mascalzoni D, Shepherd J, Taylor PL, Terry SF, Winter SF (2012) From patients to partners: participant-centric initiatives in biomedical research. Nat Rev Genet 13(5):371–376. doi:10.1038/nrg3218

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Keogh LA, Fisher D, Sheinfeld Gorin S, Schully SD, Lowery JT, Ahnen DJ, Maskiell JA, Lindor NM, Hopper JL, Burnett T, Holter S, Arnold JL, Gallinger S, Laurino M, Esplen M-J, Sinicrope PS, Colon Cancer Family R (2014) How do researchers manage genetic results in practice? The experience of the multinational Colon Cancer Family Registry. J Community Genet 5(2):99–108. doi:10.1007/s12687-013-0148-y

    Article  PubMed  PubMed Central  Google Scholar 

  • Kleinerman RA (2009) Radiation-sensitive genetically susceptible pediatric sub-populations. Pediatr Radiol 39:S27–S31. doi:10.1007/s00247-008-1015-6

    Article  PubMed  PubMed Central  Google Scholar 

  • Knoppers BM, Deschenes M, Zawati MH, Tasse AM (2013) Population studies: return of research results and incidental findings Policy Statement. Eur J Hum Genet 21(3):245–247. doi:10.1038/ejhg.2012.152

    Article  PubMed  PubMed Central  Google Scholar 

  • Kopits IM, Chen C, Roberts JS, Uhlmann W, Green RC (2011) Willingness to pay for genetic testing for Alzheimer’s disease: a measure of personal utility. Genet Test Mol Biomark 15(12):871–875. doi:10.1089/gtmb.2011.0028

    Article  Google Scholar 

  • Lerman C, Narod S, Schulman K, Hughes C, GomezCaminero A, Bonney G, Gold K, Trock B, Main D, Lynch J, Fulmore C, Snyder C, Lemon SJ, Conway T, Tonin P, Lenoir G, Lynch H (1996) BRCA1 testing in families with hereditary breast-ovarian cancer—a prospective study of patient decision making and outcomes. JAMA 275(24):1885–1892. doi:10.1001/jama.275.24.1885

    Article  PubMed  CAS  Google Scholar 

  • Lerman C, Hughes C, Trock BJ, Myers RE, Main D, Bonney A, Abbaszadegan MR, Harty AE, Franklin BA, Lynch JF, Lynch HT (1999) Genetic testing in families with hereditary nonpolyposis colon cancer. JAMA 281(17):1618–1622. doi:10.1001/jama.281.17.1618

    Article  PubMed  CAS  Google Scholar 

  • Lobb EA, Gaff C, Meiser B, Butow P, Osseiran-Moisson R, Hallowell N, kConFab I (2009) A comparison of male attendees and nonattendees at a familial cancer clinic. Genet Med 11(11):806–811. doi:10.1097/GIM.0b013e3181b780d2

    Article  PubMed  Google Scholar 

  • Lustbader ED, Williams WR, Bondy ML, Strom S, Strong LC (1992) Segregation analysis of cancer in families of childhood soft-tissue-sarcoma patients. Am J Hum Genet 51(2):344–356

    PubMed  PubMed Central  CAS  Google Scholar 

  • Masciari S, Van den Abbeele AD, Diller LR, Rastarhuyeva I, Yap J, Schneider K, Digianni L, Li FP, Fraumeni JF Jr, Syngal S, Garber JE (2008) F18-fluorodeoxyglucose-positron emission tomography/computed tomography screening in Li-Fraumeni syndrome. JAMA 299(11):1315–1319. doi:10.1001/jama.299.11.1315

    Article  PubMed  CAS  Google Scholar 

  • McBride KA, Ballinger ML, Killick E, Kirk J, Tattersall MHN, Eeles RA, Thomas DM, Mitchell G (2014) Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nat Rev Clin Oncol 11(5):260–271. doi:10.1038/nrclinonc.2014.41

    Article  PubMed  CAS  Google Scholar 

  • Meijers-Heijboer EJ, Verhoog LC, Brekelmans CTM, Seynaeve C, Tilanus-Linthorst MMA, Wagner A, Dukel L, Devilee P, van den Ouweland AMW, van Geel AN, Klijn JGM (2000) Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation. Lancet 355(9220):2015–2020. doi:10.1016/s0140-6736(00)02347-3

    Article  PubMed  CAS  Google Scholar 

  • Meiser B (2005) Psychological impact of genetic testing for cancer susceptibility: an update of the literature. Psycho-Oncology 14(12):1060–1074. doi:10.1002/pon.933

    Article  PubMed  Google Scholar 

  • Meiser B, Price MA, Butow PN, Karatas J, Wilson J, Heiniger L, Baylock B, Charles M, McLachlan S-A, Phillips K-A (2013) Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer. Familial Cancer 12(1):101–109. doi:10.1007/s10689-012-9585-8

    Article  PubMed  Google Scholar 

  • Mitchell G, Ballinger ML, Wong S, Hewitt C, James P, Young M-A, Cipponi A, Pang T, Goode DL, Dobrovic A, Thomas DM, International Sarcoma Kindred S (2013) High frequency of germline TP53 mutations in a prospective adult-onset sarcoma cohort. PLoS One 8(7):e69026. doi:10.1371/journal.pone.0069026

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Murphy J, Scott J, Kaufman D, Geller G, LeRoy L, Hudson K (2008) Public expectations for return of results from large-cohort genetic research. Am J Bioeth 8(11):36–43. doi:10.1080/15265160802513093

    Article  PubMed  PubMed Central  Google Scholar 

  • Nichols KE, Malkin D, Garber JE, Fraumeni JF, Li FP (2001) Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomark Prev 10(2):83–87

    CAS  Google Scholar 

  • O'Neill S, Peters J, Vogel V, Feingolg E, Rubinstein W (2006) Referral to cancer genetic counseling: are there stages of readiness? Am J Med Genet 142C:221–231

    Article  PubMed  Google Scholar 

  • Ormondroyd E, Moynihan C, Watson M, Foster C, Davolls S, Ardern-Jones A, Eeles R (2007) Disclosure of genetics research results after the death of the patient participant: a qualitative study of the impact on relatives. J Genet Couns 16(4):527–538. doi:10.1007/s10897-007-9088-1

    Article  PubMed  CAS  Google Scholar 

  • Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, Olivier M (2007) Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 28(6):622–629. doi:10.1002/humu.20495

    Article  PubMed  CAS  Google Scholar 

  • Quaid KA, Jessup NM, Meslin EM (2004) Disclosure of genetic information obtained through research. Genet Test 8(3):347–355. doi:10.1089/gte.2004.8.347

    Article  PubMed  Google Scholar 

  • Rice P, Ezzy D (1999) Qualitative research methods. Oxford University Press

  • Ruijs MWG, Verhoef S, Rookus MA, Pruntel R, van der Hout AH, Hogervorst FBL, Kluijt I, Sijmons RH, Aalfs CM, Wagner A, Ausems M, Hoogerbrugge N, van Asperen CJ, Garcia EBG, Meijers-Heijboer H, ten Kate LP, Menko FH, van't Veer LJ (2010) TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet 47(6):421–428. doi:10.1136/jmg.2009.073429

    Article  PubMed  CAS  Google Scholar 

  • Sexton AC, Metcalfe SA (2008) Disclosing genetic research results after death of pediatric patients. JAMA 300(14):1693–1695. doi:10.1001/jama.300.14.1693

    Article  PubMed  CAS  Google Scholar 

  • Sexton AC, Sahhar M, Thorburn DR, Metcalfe SA (2008) Impact of a genetic diagnosis of a mitochondrial disorder 5–17 years after the death of an affected child. J Genet Couns 17(3):261–273. doi:10.1007/s10897-007-9145-9

    Article  PubMed  CAS  Google Scholar 

  • Strauss A, Corbin J (1991) Basics of qualitative research. Sage, London

    Google Scholar 

  • Thorne S (2000) Data analysis in qualitative research. Br Med J 3:68–70

    Google Scholar 

  • Varley JM, Evans DGR, Birch JM (1997) Li-Fraumeni syndrome—a molecular and clinical review. Br J Cancer 76(1):1–14. doi:10.1038/bjc.1997.328

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, Novokmet A, Finlay J, Malkin D (2011) Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol 12(6):559–567. doi:10.1016/s1470-2045(11)70119-x

    Article  PubMed  CAS  Google Scholar 

  • Wakefield CE, Ratnayake P, Meiser B, Suthers G, Price MA, Duffy J, Tucker K, Kathleen Cuningham Natl C (2011) “For all my family’s sake, I should go and find out”: an Australian report on genetic counseling and testing uptake in individuals at high risk of breast and/or ovarian cancer. Genet Test Mol Biomark 15(6):379–385. doi:10.1089/gtmb.2010.0158

    Article  Google Scholar 

  • Wakefield CE, Thorne H, Kirk J, Niedermayr E, Doolan EL, Tucker K, Kathleen Cuningham Natl C (2013) Improving mutation notification when new genetic information is identified in research: a trial of two strategies in familial breast cancer. Genet Med 15(3):187–194. doi:10.1038/gim.2012.115

    Article  PubMed  Google Scholar 

  • Warner BJ, Curnow LJ, Polglase AL, Debinski HS (2005) Factors influencing uptake of genetic testing for colorectal cancer risk in an Australian Jewish population. J Genet Couns 14(5):387–394. doi:10.1007/s10897-005-1623-3

    Article  PubMed  CAS  Google Scholar 

  • Young M-A, Herlihy A, Mitchell G, Thomas DM, Ballinger M, Tucker K, Lewis CR, Neuhaus S, Halliday J, International Sarcoma Kindred S (2013) The attitudes of people with sarcoma and their family towards genomics and incidental information arising from genetic research. Clin Sarcoma Res 3(1):11. doi:10.1186/2045-3329-3-11

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu JH, Jamal SM, Tabor HK, Bamshad MJ (2013) Self-guided management of exome and whole-genome sequencing results: changing the results return model. Genet Med 15(9):684–690. doi:10.1038/gim.2013.35

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was funded by The Johanna Sewell Sarcoma Research Award to Mary-Anne Young, Nina Hallowell and Gillian Mitchell with a Postgraduate Scholarship for Kate McBride provided by the National Health and Medical Research Council, Australia.

Compliance with ethics guidelines

ᅟ

Conflict of interest

Kate McBride, Nina Hallowell, Judy Kirk, Mandy Ballinger, David Thomas, Gillian Mitchell and Mary-Anne Young declare no conflict of interest.

Ethics compliance

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Author information

Authors and Affiliations

  1. School of Public Health, Sydney Medical School, Camperdown, NSW, 2006, Australia

    Kate A. McBride

  2. The Familial Cancer Service, Crown Princess Mary Cancer Centre, Westmead, NSW, 2145, Australia

    Kate A. McBride & Judy Kirk

  3. Centre for Health and Society, University of Melbourne, Parkville, VIC, 3052, Australia

    Nina Hallowell

  4. Department of Cancer Medicine, Sydney Medical School, Royal Prince Alfred Hospital, Camperdown, NSW, 2006, Australia

    Martin H. N. Tattersall

  5. Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC, 3002, Australia

    Mandy L. Ballinger

  6. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, 3052, Australia

    Mandy L. Ballinger & Gillian Mitchell

  7. The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia

    David M. Thomas

  8. Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, VIC, 3002, Australia

    Gillian Mitchell & Mary-Anne Young

Authors
  1. Kate A. McBride
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nina Hallowell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin H. N. Tattersall
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Judy Kirk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mandy L. Ballinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David M. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gillian Mitchell
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mary-Anne Young
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kate A. McBride.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

McBride, K.A., Hallowell, N., Tattersall, M.H.N. et al. Timing and context: important considerations in the return of genetic results to research participants. J Community Genet 7, 11–20 (2016). https://doi.org/10.1007/s12687-015-0231-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12687-015-0231-7

Keywords

Search

Navigation