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Catechol-O-methyltransferase haplotypes and breast cancer among women on Long Island, New York

  • Epidemiology
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Abstract

The gene encoding catechol-O-methyltransferase (COMT), critical to the inactivation of reactive catechol estrogens, has several single nucleotide polymorphisms (SNPs) that influence enzyme activity. A 3-SNP haplotype (IVS1+255 C>T; Ex4-12 G>A; 3′UTR-521 A>G), which has been shown to reduce COMT expression in the human brain, has been identified. To evaluate the influence of genetic variation of COMT on breast cancer risk, these 3-SNPs were genotyped in 1052 cases and 1098 controls. We estimated the associations between breast cancer and individual SNPs, as well as, multilocus haplotypes. We also examined surrogates of hormone exposure as potential modifiers of the putatively functional Ex4-12 SNP-breast cancer association. Odds ratios (OR) and 95% confidence intervals (CI) were based on age-adjusted unconditional logistic regression models. We found no association between the individual SNPs alone and breast cancer. When examining the association between breast cancer and the 3-SNP haplotypes, we observed a 19% increase in risk associated with each copy of the TGG haplotype (OR=1.19, 95% CI 0.96–1.49), relative to the common TAA haplotype, which was statistically significant when assuming a dominant model (OR=1.32, 95% CI 1.05–1.67, p-value=0.02). In this report of COMT haplotypes and breast cancer, we found some evidence that additional genetic variability beyond the Ex4-12 G>A SNP contributes to risk of breast cancer among a small subgroup of women; however, these results need to be replicated in additional studies.

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Acknowledgements

For their insightful advice, the authors wish to thank Drs. Montserrat Garcia-Closas, Sonja Berndt, Stephanie Engel, Ulrike Peters, and Dirk Petersen. For their valuable contributions to the Long Island Breast Cancer Study Project the authors thank: members of the Long Island Breast Cancer Network; the 31 participating institutions on Long Island and in New York City, NY; our National Institutes of Health collaborators, Gwen Colman, Ph.D., National Institutes of Environmental Health Sciences; G. Iris Obrams, M.D., Ph.D. formerly of the National Cancer Institute; members of the External Advisory Committee to the population-based case–control study: Leslie Bernstein, Ph.D., (Committee chair); Gerald Akland, M.S.; Barbara Balaban, MSW; Blake Cady, M.D.; Dale Sandler, Ph.D.; Roy Shore, Ph.D.; and Gerald Wogan, Ph.D.; as well as other collaborators who assisted with various aspects of our data collection efforts including Mary Wolff, Ph.D.; Steve Stellman, Ph.D.; Maureen Hatch, Ph.D.; Gail Garbowski, MPH; H. Leon Bradlow, Ph.D.; David Camann, B.S.; Martin Trent, B.S.; Jan Beyea, Ph.D.; Ruby Senie, Ph.D.; Carla Maffeo, Ph.D.; Pat Montalvan; Gertrud Berkowitz, Ph.D.; Margaret Kemeny, M.D.; Mark Citron, M.D.; Freya Schnabel, M.D.; Allen Schuss, M.D.; Steven Hajdu, M.D.; and Vincent Vinceguerra, M.D. This work was supported in part by grants from the National Cancer Institute and the National Institutes of Environmental Health and Sciences (Grant nos. UO1CA/ES66572, UO1CA66572, P50CA55283, P30ES09089, and P30ES10126), the Department of Defense (Grant no. BC021366), and the University of North Carolina Lineberger Comprehensive Cancer Center Breast Cancer SPORE (Grant no. P50CA58223).

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hil, NC, 27516, USA

    Mia M. Gaudet, Jeannette T. Bensen, Jane Schroeder, Andrew F. Olshan & Marilie D. Gammon

  2. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA

    Mary Beth Terry & Alfred I. Neugut

  3. Global Epidemiology, Worldwide Safety and Risk Management, Pfizer, Inc., New York, NY, 10017, USA

    Sybil M. Eng

  4. Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Susan L. Teitelbaum & Julie A. Britton

  5. BioServe Biotechnologies, Ltd., Laurel, MD, 20707, USA

    Teresa A. Lehman

  6. Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA

    Alfred I. Neugut

  7. Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, NY, 14222, USA

    Christine B. Ambrosone

  8. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA

    Regina M. Santella

  9. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., EPS/7055, Bethesda, MD, 20852, USA

    Mia M. Gaudet

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  1. Mia M. Gaudet
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  2. Jeannette T. Bensen
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  3. Jane Schroeder
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  5. Mary Beth Terry
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  6. Sybil M. Eng
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  7. Susan L. Teitelbaum
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  8. Julie A. Britton
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  9. Teresa A. Lehman
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  10. Alfred I. Neugut
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  11. Christine B. Ambrosone
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  13. Marilie D. Gammon
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Correspondence to Mia M. Gaudet.

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Gaudet, M.M., Bensen, J.T., Schroeder, J. et al. Catechol-O-methyltransferase haplotypes and breast cancer among women on Long Island, New York. Breast Cancer Res Treat 99, 235–240 (2006). https://doi.org/10.1007/s10549-006-9205-0

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