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

  • Epidemiology
  • Published:
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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.

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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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Authors and Affiliations

  1. Cancer Prevention Detection and Control Research Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, 27705, USA

    Patricia G. Moorman, Frances Wang & Joellen M. Schildkraut

  2. Department of Statistical Science, Duke University, Durham, NC, 27705, USA

    Edwin S. Iversen

  3. Division of Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, 27705, USA

    P. Kelly Marcom

  4. Department of Surgery, Duke University Medical Center, Durham, NC, 27705, USA

    Jeffrey R. Marks

  5. Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Eunjung Lee & Giske Ursin

  6. Department of Nutrition, University of Oslo, Oslo, Norway

    Giske Ursin

  7. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA

    Timothy R. Rebbeck

  8. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    Timothy R. Rebbeck & Susan M. Domchek

  9. Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA, USA

    Susan M. Domchek

  10. Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Banu Arun

  11. School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA

    Lisa Susswein

  12. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA

    Claudine Isaacs

  13. Department of Medical Oncology and Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA

    Judy E. Garber

  14. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Kala Visvanathan

  15. School of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Kala Visvanathan & Constance A. Griffin

  16. Department of Pediatrics, University of South Florida, Tampa, FL, USA

    Rebecca Sutphen

  17. Moffitt Cancer Center, Tampa, FL, USA

    Jennifer Brzosowicz

  18. Division of Molecular Medicine & Genetics, University of Michigan, Ann Arbor, MI, USA

    Stephen Gruber

  19. Harvard School of Public Health and Harvard Medical School, Boston, MA, USA

    Dianne M. Finkelstein

Authors
  1. Patricia G. Moorman
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  2. Edwin S. Iversen
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  3. P. Kelly Marcom
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  4. Jeffrey R. Marks
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  5. Frances Wang
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  6. Eunjung Lee
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  7. Giske Ursin
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  8. Timothy R. Rebbeck
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  9. Susan M. Domchek
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  10. Banu Arun
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  11. Lisa Susswein
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  12. Claudine Isaacs
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  13. Judy E. Garber
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  14. Kala Visvanathan
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  15. Constance A. Griffin
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  16. Rebecca Sutphen
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  17. Jennifer Brzosowicz
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  18. Stephen Gruber
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  19. Dianne M. Finkelstein
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  20. Joellen M. Schildkraut
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Consortia

Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab)

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Correspondence to Patricia G. Moorman.

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Moorman, P.G., Iversen, E.S., Marcom, P.K. et al. Evaluation of established breast cancer risk factors as modifiers of BRCA1 or BRCA2: a multi-center case-only analysis. Breast Cancer Res Treat 124, 441–451 (2010). https://doi.org/10.1007/s10549-010-0842-y

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  • DOI: https://doi.org/10.1007/s10549-010-0842-y

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