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Breast Cancer Research and Treatment

, Volume 124, Issue 2, pp 441–451 | Cite as

Evaluation of established breast cancer risk factors as modifiers of BRCA1 or BRCA2: a multi-center case-only analysis

  • Patricia G. MoormanEmail author
  • Edwin S. Iversen
  • P. Kelly Marcom
  • Jeffrey R. Marks
  • Frances Wang
  • Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab)
  • Eunjung Lee
  • Giske Ursin
  • Timothy R. Rebbeck
  • Susan M. Domchek
  • Banu Arun
  • Lisa Susswein
  • Claudine Isaacs
  • Judy E. Garber
  • Kala Visvanathan
  • Constance A. Griffin
  • Rebecca Sutphen
  • Jennifer Brzosowicz
  • Stephen Gruber
  • Dianne M. Finkelstein
  • Joellen M. Schildkraut
Epidemiology

Abstract

The incomplete penetrance of mutations in BRCA1 and BRCA2 suggests that some combination of environmental and genetic factors modifies the risk of breast cancer in mutation carriers. This study sought to identify possible interactions between established breast cancer risk factors and BRCA1 or BRCA2 mutations using a case-only study design. Breast cancer cases that had been tested for BRCA1 and BRCA2 mutations were identified from 11 collaborating centers. Comparisons of reproductive and lifestyle risk factors were made between women with breast cancer who were positive for BRCA1 mutations (n = 283), BRCA2 mutations (n = 204), or negative for both BRCA1 and BRCA2 mutations (n = 894). Interaction risk ratios (IRRs) were calculated using multinominal logistic regression models. Compared with non-carriers, statistically significant IRRs were observed for later age at menarche among BRCA2 mutation carriers, for a greater number of pregnancies among both BRCA1 and BRCA2 mutation carriers, and for alcohol use among BRCA1 mutation carriers. Our data suggest that the risk for breast cancer among BRCA1 or BRCA2 carriers may be modified by reproductive characteristics and alcohol use. However, our results should be interpreted cautiously given the overall inconsistency in the epidemiologic literature on modifiers of BRCA1 and BRCA2.

Keywords

Breast cancer BRCA1 BRCA2 Mutations Modifiers 

Notes

Acknowledgments

This study was funded by the following grants and contracts from the National Cancer Institute, National Institutes of Health: P50-CA068438 Specialized Program of Research Excellence (SPORE) in breast cancer, Duke University Medical Center; Cancer Genetics Network (U01 CA78284 and HHSN261200744000C), Massachusetts General Hospital.

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Patricia G. Moorman
    • 1
    Email author
  • Edwin S. Iversen
    • 2
  • P. Kelly Marcom
    • 3
  • Jeffrey R. Marks
    • 4
  • Frances Wang
    • 1
  • Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab)
    • 5
  • Eunjung Lee
    • 6
  • Giske Ursin
    • 6
    • 7
  • Timothy R. Rebbeck
    • 8
    • 9
  • Susan M. Domchek
    • 9
    • 10
  • Banu Arun
    • 11
  • Lisa Susswein
    • 12
  • Claudine Isaacs
    • 13
  • Judy E. Garber
    • 14
  • Kala Visvanathan
    • 15
    • 16
  • Constance A. Griffin
    • 16
  • Rebecca Sutphen
    • 17
  • Jennifer Brzosowicz
    • 18
  • Stephen Gruber
    • 19
  • Dianne M. Finkelstein
    • 20
  • Joellen M. Schildkraut
    • 1
  1. 1.Cancer Prevention Detection and Control Research Program, Department of Community and Family MedicineDuke University Medical CenterDurhamUSA
  2. 2.Department of Statistical ScienceDuke UniversityDurhamUSA
  3. 3.Division of Oncology, Department of MedicineDuke University Medical CenterDurhamUSA
  4. 4.Department of SurgeryDuke University Medical CenterDurhamUSA
  5. 5.Peter MacCallum Cancer CentreEast MelbourneAustralia
  6. 6.Department of Preventive MedicineUniversity of Southern California Keck School of MedicineLos AngelesUSA
  7. 7.Department of NutritionUniversity of OsloOsloNorway
  8. 8.Department of Biostatistics and EpidemiologyUniversity of PennsylvaniaPhiladelphiaUSA
  9. 9.Abramson Cancer Center, University of PennsylvaniaPhiladelphiaUSA
  10. 10.Division of Hematology-OncologyUniversity of PennsylvaniaPhiladelphiaUSA
  11. 11.Breast Medical Oncology and Clinical Cancer GeneticsThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  12. 12.School of MedicineUniversity of North Carolina-Chapel HillChapel HillUSA
  13. 13.Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonUSA
  14. 14.Department of Medical Oncology and Population SciencesDana Farber Cancer InstituteBostonUSA
  15. 15.Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreUSA
  16. 16.School of MedicineJohns Hopkins UniversityBaltimoreUSA
  17. 17.Department of PediatricsUniversity of South FloridaTampaUSA
  18. 18.Moffitt Cancer CenterTampaUSA
  19. 19.Division of Molecular Medicine & GeneticsUniversity of MichiganAnn ArborUSA
  20. 20.Harvard School of Public Health and Harvard Medical SchoolBostonUSA

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