title: Catechol-O-methyltransferase haplotypes and breast cancer among women on Long Island, New York.
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.
authors.affiliation: Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hil, NC 27516, USA. gaudetm@mail.nih.gov
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Jeannette T
authors.initials: JT
authors.lastname: Bensen
authors.forename: Jane
authors.initials: J
authors.lastname: Schroeder
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.forename: Sybil M
authors.initials: SM
authors.lastname: Eng
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.forename: Julie A
authors.initials: JA
authors.lastname: Britton
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Lehman
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009518:New York / Q000453:epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D002394:Catechol O-Methyltransferase