Familial Cancer

, Volume 5, Issue 1, pp 3–13

Partnering in Oncogenetic Research – The INHERIT BRCAs Experience: Opportunities and Challenges

  • Denise Avard
  • Peter Bridge
  • Lucie M. Bucci
  • Jocelyne Chiquette
  • Michel Dorval
  • Francine Durocher
  • Doug Easton
  • Béatrice Godard
  • David Goldgar
  • Bartha Maria Knoppers
  • Rachel Laframboise
  • Bernard Lespérance
  • Marie Plante
  • Sean V. Tavtigian
  • Hélène Vézina
  • Brenda Wilson
  • INHERIT BRCAs
  • Jacques Simard
Article

Abstract

Today it is common to conduct research in collaboration with colleagues from different disciplines and institutions. The INterdisciplinary HEalth Research International Team on BReast CAncer susceptibility (INHERIT BRCAs), involves Canadian and international experts from diverse fields working with health service providers, patients and collaborators from the World Health Organization and other European networks. Evidence-based information and knowledge transfer drive our efforts to advance genomic research to understand the genetic basis of cancer susceptibility and treatment response. Several goals reveal the interdisciplinary team approach: (a) to estimate the prevalence and penetrance of BRCA1 and BRCA2 mutations and their deleterious impact upon different populations; (b) to pinpoint novel breast cancer susceptibility loci; (c) to assess the efficacy of clinical interventions; (d) to address changes in quality of life and health-related behaviour from the decision to undergo genetics testing and during follow-up; (e) to evaluate legal, social and ethical implications; and, finally; (f) to promote professional and public education by facilitating the transfer of research findings to clinical practice and informing policy makers. The lessons learned by the INHERIT research team and future challenges are presented.

Keywords

academic teams clinical practice collaboration familial cancer genetics hereditary cancer interdisciplinary knowledge translation research 

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References

  1. 1.
    Ford, D, Easton, DF, Stratton, M,  et al. 1998Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage ConsortiumAm J Hum Genet6267689CrossRefPubMedGoogle Scholar
  2. 2.
    Department of Health2003Genetics White Paper: Our Inheritance, Our Future – Realising the Potential of Genetics in the National Health SystemDepartment of HealthLondon, UKGoogle Scholar
  3. 3.
    Khoury, MJ, Burke, W, Thomson, EJ 2000Genetics and Public Health in the 21st Century. Using Genetic Information to Improve Health and Prevent DiseaseOxford University PressOxfordGoogle Scholar
  4. 4.
    Khoury, MJ, Little, J, Burke, W 2004Human Genome Epidemiology: A Scientific Foundation for Using Genetic Information to Improve Health and Prevent DiseaseOxford University PressOxfordGoogle Scholar
  5. 5.
    Lippman, SM, Levin, B, Brenner, DE,  et al. 2004Cancer prevention and the American Society of Clinical OncologyJ Clin Oncol22384851CrossRefPubMedGoogle Scholar
  6. 6.
    Guttmacher, AE, Collins, FS, Carmona, RH 2004The family history – more important than everN Engl J Med35123336CrossRefPubMedGoogle Scholar
  7. 7.
    Hemminki, K, Eng, C 2004Clinical genetic counselling for familial cancers requires reliable data on familial cancer risks and general action plansJ Med Genet418017CrossRefPubMedGoogle Scholar
  8. 8.
    Nathanson, KL, Wooster, R, Weber, BL 2001Breast cancer genetics: What we know and what we needNat Med75526CrossRefPubMedGoogle Scholar
  9. 9.
    Ponder, BA 2001Cancer geneticsNature41133641CrossRefPubMedGoogle Scholar
  10. 10.
    Horwitz, AR 2003Building bridges through collaboration – a pathway for interdisciplinary researchTrends Cell Biol1323CrossRefPubMedGoogle Scholar
  11. 11.
    O’Connor, GC, Rice, MP, Peters, L, Veryzer, JG 2003Managing interdisciplinary, longitudinal research teams: Extending grounded theory-building methodologiesOrg Sci1435373Google Scholar
  12. 12.
    Klein, JT 1990Interdisciplinarity: History, Theory and PracticeWayne State University PressDetroit, MIGoogle Scholar
  13. 13.
    Qin, J, Lancaster, FW, Allen, B 1997Types and levels of collaboration in interdisciplinary research in the sciencesJournal of the American Society for Information Science48893916CrossRefGoogle Scholar
  14. 14.
    Metzger, N, Zare, RN 1999Interdisciplinary research: From belief to realityScience2836423CrossRefGoogle Scholar
  15. 15.
    Altshuler, JS, Altshuler, D 2004Organizational challenges in clinical genomic researchNature42947881CrossRefPubMedGoogle Scholar
  16. 16.
    Lomas, J 2000Connecting research and policyCan J Policy Res11404Google Scholar
  17. 17.
    Lenfant, C 2003Shattuck lecture – clinical research to clinical practice – lost in translation?N Engl J Med34986874CrossRefPubMedGoogle Scholar
  18. 18.
    Forbes, A, Griffiths, P 2002Methodological strategies for the identification and synthesis of ‘evidence’ to support decision-making in relation to complex healthcare systems and practicesNurs Inq914155CrossRefPubMedGoogle Scholar
  19. 19.
    Vogelstein, B, Kinzler, KW 2004Cancer genes and the pathways they controlNat Med1078999CrossRefPubMedGoogle Scholar
  20. 20.
    Pharoah, PD, Antoniou, A, Bobrow, M,  et al. 2002Polygenic susceptibility to breast cancer and implications for preventionNat Genet31336CrossRefPubMedGoogle Scholar
  21. 21.
    Pharoah, PD, Dunning, AM, Ponder, BA, Easton, DF 2004Association studies for finding cancer-susceptibility genetic variantsNat Rev Cancer485060CrossRefPubMedGoogle Scholar
  22. 22.
    Narod, SA 2002Modifiers of risk of hereditary breast and ovarian cancerNat Rev Cancer211323CrossRefPubMedGoogle Scholar
  23. 23.
    Jernstrom, H, Lubinski, J, Lynch, HT,  et al. 2004Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriersJ Natl Cancer Inst9610948PubMedGoogle Scholar
  24. 25.
    Antoniou, AC, Easton, DF 2003Polygenic inheritance of breast cancer: Implications for design of association studiesGenet Epidemiol25190202CrossRefPubMedGoogle Scholar
  25. 26.
    Smith P, Spurdle A, Harrington PA et al. Analysis of polymorphisms in DNA repair genes as modifiers of breast cancer risk in BRCA1 and BRCA2 carriers. The American Society of Human Genetics, 54th Annual Meeting, October 26–30, 2004, Toronto, Ontario, Canada. Abstract #438, p. 100.Google Scholar
  26. 27.
    Simard J, Dumont M, Moisan A-M et al. Molecular epidemiology of BRCA1 and BRCA2 mutations in French Canadian breast/ovarian families. The American Society of Human Genetics, 54th Annual Meeting, October 26–30, 2004, Toronto, Ontario, Canada. Abstract #480, p. 107.Google Scholar
  27. 28.
    Goldgar, D, Easton, D, Deffenbaugh, A,  et al. 2004Integrated evaluation of DNA sequence variants of unknown clinical significance: Application to BRCA1 and BRCA2Am J Hum Genet7553544CrossRefPubMedGoogle Scholar
  28. 29.
    Serova, OM, Mazoyer, S, Puget, N,  et al. 1997Mutations in BRCA1 and BRCA2 in breast cancer families: Are there more breast cancer-susceptibility genes?Am J Hum Genet6048695PubMedGoogle Scholar
  29. 30.
    Antoniou, AC, Easton, DF 2003Polygenic inheritance of breast cancer: Implications for design of association studiesGenet Epidemiol25190202CrossRefPubMedGoogle Scholar
  30. 31.
    Thompson, D, Witte, JS, Slattery, M, Goldgar, D 2004Increased power for case–control studies of single nucleotide polymorphisms through incorporation of family history and genetic constraintsGenet Epidemiol2721524CrossRefPubMedGoogle Scholar
  31. 32.
    Scriver, CR 2001Human genetics: Lessons from Quebec populationsAnnu Rev Genom Hum Genet269101Google Scholar
  32. 33.
    Vézina, H, Durocher, F, Dumont, M, Houde, L,  et al. 2005Molecular and Genealogical Characterization of the R1443X-BRCA1 Mutation in High-risk French-Canadian Breast/Ovarian Cancer FamiliesHum Genet117119132PubMedGoogle Scholar
  33. 34.
    McNally, E, Cambon-Thomsen, A 2004Ethical, Legal and Social Aspects of Genetic Testing: Research, Development and Clinical ApplicationsEuropean CommissionBrusselsGoogle Scholar
  34. 35.
    Einbeigi, Z, Bergman, A, Karlsson, P,  et al. 2003Population study on BRCA1/2 mutations in women with breast and ovarian cancer in western SwedenBreast12S17Google Scholar
  35. 36.
    Inoue, R, Ushijima, T, Fukutomi, T,  et al. 1997BRCA2 germline mutations in Japanese breast cancer familiesInt J Cancer74199204CrossRefPubMedGoogle Scholar
  36. 37.
    Eccles, DM 2003Genetic testing for BRCA1 mutation in the UKLancet3611789CrossRefPubMedGoogle Scholar
  37. 38.
    Burke, W, Daly, M, Garber, J,  et al. 1997Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies ConsortiumJAMA2779971003CrossRefPubMedGoogle Scholar
  38. 39.
    Noorani HZ, McGahan L. Predictive Genetic Testing for Breast and Prostate Cancer. Ottawa, Canada: Canadian Coordinating Office for Health and Technology Assessment (CCOHTA) 1999; Report No. 4.Google Scholar
  39. 40.
    Goldgar D, Bonnardel C, Renard H, Yaqoubi O. The International BRCA1/2 Carrier Cohort Study: Purpose, Rationale and study design. Breast Cancer Res 2000; 2: e010.Google Scholar
  40. 41.
    Baum, A, Friedman, AL, Zakowski, SG 1997Stress and genetic testing for disease riskHealth Psychol16819CrossRefPubMedGoogle Scholar
  41. 42.
    Dorval, M, Maunsell, E, Dugas, MJ, Simard, J 2001Support groups for people carrying a BRCA mutationCMAJ165740PubMedGoogle Scholar
  42. 43.
    Dorval M, Maunsell E, Patenaude AF et al. Elapsed time to disclosure of BRCA1/2 genetic testing result and participants’ distress: Preliminary finding from a research setting. Psycho-Oncology 2000; 9(5 Suppl) abstract #341.Google Scholar
  43. 44.
    Dorval M, Gauthier G, Maunsell E et al. Are women with an inconclusive BRCA1/2 genetic tests result falsely reassured? Psycho-Oncology 2003; 124(4 Suppl).Google Scholar
  44. 45.
    Dorval, M, Morel, S, Maunsell, E,  et al. 2003When using the Impact of Events Scale to assess psychological distress in the context of BRCA1/2 testing, does the event matter?Psycho-Oncology12307Google Scholar
  45. 46.
    Dorval M, Davilmar A, Rouleau I et al. Men undergoing BRCA1/2 genetic testing: Who are they and why do they do it? Psycho-Oncology 2005; 14(s85).Google Scholar
  46. 47.
    Rouleau, I, Chiquette, J, Plante, M,  et al. 2004Changes in health-related behaviours following BRCA 1/2 genetic testing: The case of hormone replacement therapyJ Obstet Gynaecol Can26105966PubMedGoogle Scholar
  47. 48.
    Vallee, MH, Rouleau, I, Plante, M,  et al. 2005Hormone therapy use among women tested for BRCA1/2 mutations following the publication of the Women’s Health Initiative Study resultsJ Obstet Gynaecol Can27321PubMedGoogle Scholar
  48. 49.
    Wilson, BJ, Forrest, K, Teijlingen, ER,  et al. 2004Family communication about genetic risk: The little that is knownGenetics71524Google Scholar
  49. 50.
    Lemmens, T, Joly, Y, Knoppers, BM 2004Genetics and life insurance: A comparative approachGenEdit2115Google Scholar
  50. 51.
    Clayton, EW 2004

    Policy challenges ethical, legal, and social implications of genetics

    Magill,  eds. Genetic and Ethics An Interdisciplinary StudySaint Louis University PressSaint Louis2334
    Google Scholar
  51. 52.
    World Health Organization1997Statement of WHO Expert Advisory Group on Ethical Issues in Medical GeneticsWHOGenevaGoogle Scholar
  52. 53.
    Knoppers, BM, Joly, Y 2004Physicians, genetics and life insuranceCMAJ17014213PubMedGoogle Scholar
  53. 54.
    Skene, L 1998Patients’ rights or family responsibilities? Two approaches to genetic testingMed Law Rev6141PubMedGoogle Scholar
  54. 55.
    Letendre, M, Godard, B 2004Expanding the physician’s duty of care: A duty to recontact?Med Law235319PubMedGoogle Scholar
  55. 56.
    Benkendorf, JL, Reutenauer, JE, Hughes, CA,  et al. 1997Patients’ attitudes about autonomy and confidentiality in genetic testing for breast–ovarian cancer susceptibilityAm J Med Genet73296303CrossRefPubMedGoogle Scholar
  56. 57.
    Birdsell, J, Atkinson-Grosjean, J, Landry, R 2002Knowledge Translation in Two New Programs: Achieving the ‘Pasteur Effect’Canadian Institutes of Health ResearchOttawaGoogle Scholar
  57. 58.
    Shaw, C, McIntosh, A, Evans, G,  et al. 2004Clinical Guidelines and Evidence Review for the Classification and Care of Women at Risk of Familial Breast CancerNational Collaborating Centre for Primary Care/University of SheffieldLondonGoogle Scholar
  58. 59.
    Eisinger, F, Bressac, B, Castaigne, D,  et al. 2004Identification and management of hereditary predisposition to cancer of the breast and the ovary – update 2004Bull Cancer9121937PubMedGoogle Scholar
  59. 60.
    Grimshaw, JM, Thomas, RE, MacLennan, G,  et al. 2004Effectiveness and efficiency of guideline dissemination and implementation strategiesHealth Technol Assess8iii72PubMedGoogle Scholar
  60. 61.
    Carlow, DR 2000Status report: Canadian association of provincial cancer agenciesChronic Diseases Canada21303Google Scholar
  61. 62.
    Vasen, HF, Haites, NE, Evans, DG,  et al. 1998Current policies for surveillance and management in women at risk of breast and ovarian cancer: A survey among 16 European family cancer clinics. European Familial Breast Cancer Collaborative GroupEur J Cancer3419226CrossRefPubMedGoogle Scholar
  62. 63.
    World Health Organization1997Proposed International Guidelines on Ethical Issues in Medical Genetics and Genetic Service. Report of a WHO Meeting on Ethical Issues in Medical GeneticsWorld Health OrganizationGenevaGoogle Scholar
  63. 64.
    World Health Organization. Control of Hereditary Diseases. Geneva: WHO 1996; Report No. 865.Google Scholar
  64. 65.
    Emery, J, Lucassen, A, Murphy, M 2001Common hereditary cancers and implications for primary careLancet3585663CrossRefPubMedGoogle Scholar
  65. 66.
    The New York State Task Force on Life and the Law2000Integrating Genetic Services into Clinical Care. Genetic Testing and Screening in the Age of Genomic MedicineThe New York State Task Force on Life and the LawNew York34786Google Scholar
  66. 67.
    Bayley, C 2004

    The challenge of physician education in genetics

    Magill, G eds. Genetics and Ethics: An Interdisciplinary StudySaint Louis University PressSaint Louis17685
    Google Scholar
  67. 68.
    GEOQ. Goupe d’Etude en Oncologie du Quebec 2005. Ref Type: Internet Communication.Google Scholar
  68. 69.
    Yoon, PW, Scheuner, MT, Khoury, MJ 2003Research priorities for evaluating family history in the prevention of common chronic diseasesAm J Prev Med2412835CrossRefPubMedGoogle Scholar
  69. 70.
    Antoniou, A, Pharoah, PD, Narod, S,  et al. 2003Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: A combined analysis of 22 studiesAm J Hum Genet72111730CrossRefPubMedGoogle Scholar
  70. 71.
    Goldgar, DE, Easton, DF, Deffenbaugh, AM,  et al. 2004Integrated evaluation of DNA sequence variants of unknown clinical significance: Application to BRCA1 and BRCA2Am J Hum Genet7553544CrossRefPubMedGoogle Scholar
  71. 72.
    Antoniou, AC, Easton, DF 2003Polygenic inheritance of breast cancer: Implications for design of association studiesGenet Epidemiol25190202CrossRefPubMedGoogle Scholar
  72. 73.
    CHEK2*1100delC and susceptibility to breast cancer: A collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 2004; 74(6): 1175–82.Google Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • Denise Avard
    • 1
    • 17
  • Peter Bridge
    • 2
  • Lucie M. Bucci
    • 1
  • Jocelyne Chiquette
    • 3
  • Michel Dorval
    • 4
  • Francine Durocher
    • 5
  • Doug Easton
    • 6
  • Béatrice Godard
    • 1
    • 7
  • David Goldgar
    • 8
  • Bartha Maria Knoppers
    • 1
    • 9
  • Rachel Laframboise
    • 10
  • Bernard Lespérance
    • 11
  • Marie Plante
    • 12
  • Sean V. Tavtigian
    • 13
  • Hélène Vézina
    • 14
  • Brenda Wilson
    • 15
  • INHERIT BRCAs
  • Jacques Simard
    • 5
    • 16
  1. 1.Centre de Recherche en Droit Public, Faculty of LawUniversity of MontrealMontrealCanada
  2. 2.Molecular Diagnostic Laboratory, Alberta Children’s Hospital, Departments of Medical Genetics and Pathology, Faculty of MedicineUniversity of CalgaryCalgaryCanada
  3. 3.Clinique des Maladies du Sein Deschênes-FabiaHôpital du Saint-SacrementCanada
  4. 4.Unité de Recherche en Santé des Populations, CHA Research Center, Hôpital du Saint-Sacrement, Faculty of PharmacyLaval UniversityCanada
  5. 5.Cancer Genomics Laboratory, CHUL Research Centre, CHUQ, Department of Anatomy and Physiology, Faculty of MedicineLaval UniversityCanada
  6. 6.CRC Genetic Epidemiology Unit, Strangeways Research LaboratoriesUniversity of CambridgeCambridgeUK
  7. 7.Faculty of MedicineUniversity of MontrealMontrealCanada
  8. 8.Genetic Epidemiology Unit, International Agency for Research on CancerWorld Health OrganizationLyonFrance
  9. 9.Canada Research Chair in Law and MedicineCanada
  10. 10.Clinical Genetics Division, Department of Paediatrics and Medicine, CHUL, CHUQ, Faculty of MedicineLaval UniversityCanada
  11. 11.Department of Haemato-Oncology, Hôpital du Sacré-Coeur de Montréal, Faculty of MedicineUniversity of MontrealMontrealCanada
  12. 12.Gynaecology Service, Gynaecologic Oncology Division, Hôtel-Dieu de Québec, CHUQ, Department of Obstetrics and Gynaecology, Faculty of MedicineLaval UniversityCanada
  13. 13.Unit of Genetic Cancer Susceptibility, International Agency for Research on CancerWorld Health OrganizationLyonFrance
  14. 14.Department of Human Sciences, Interdisciplinary Research Group in Genetic Demography and Epidemiology (GRIG)Université du Québec à ChicoutimiChicoutimiCanada
  15. 15.Department of Epidemiology and Community MedicineUniversity of OttawaOttawaCanada
  16. 16.Canada Research Chair in OncogeneticsCanada
  17. 17.Centre de Recherche en Droit Public, Faculty of LawUniversity of MontrealMontrealCanada

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