Breast Cancer Research and Treatment

, Volume 99, Issue 2, pp 235–240

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

  • Mia M. Gaudet
  • Jeannette T. Bensen
  • Jane Schroeder
  • Andrew F. Olshan
  • Mary Beth Terry
  • Sybil M. Eng
  • Susan L. Teitelbaum
  • Julie A. Britton
  • Teresa A. Lehman
  • Alfred I. Neugut
  • Christine B. Ambrosone
  • Regina M. Santella
  • Marilie D. Gammon
Epidemiology

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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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Mia M. Gaudet
    • 1
    • 9
  • Jeannette T. Bensen
    • 1
  • Jane Schroeder
    • 1
  • Andrew F. Olshan
    • 1
  • Mary Beth Terry
    • 2
  • Sybil M. Eng
    • 3
  • Susan L. Teitelbaum
    • 4
  • Julie A. Britton
    • 4
  • Teresa A. Lehman
    • 5
  • Alfred I. Neugut
    • 2
    • 6
  • Christine B. Ambrosone
    • 7
  • Regina M. Santella
    • 8
  • Marilie D. Gammon
    • 1
  1. 1.Department of Epidemiology, School of Public HealthUniversity of North CarolinaChapel HilUSA
  2. 2.Department of Epidemiology, Mailman School of Public HealthColumbia UniversityNew YorkUSA
  3. 3.Global Epidemiology, Worldwide Safety and Risk ManagementPfizer, Inc.New YorkUSA
  4. 4.Department of Community and Preventive MedicineMount Sinai School of MedicineNew YorkUSA
  5. 5.BioServe Biotechnologies, Ltd.LaurelUSA
  6. 6.Department of Medicine, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  7. 7.Department of EpidemiologyRoswell Park Cancer InstituteBuffaloUSA
  8. 8.Department of Environmental Health Sciences, Mailman School of Public HealthColumbia UniversityNew YorkUSA
  9. 9.Division of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaUSA

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