title: An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer.
abstract: Mounting evidence suggests that catechol metabolites of estradiol may contribute to the development of estrogen-induced cancers. O-Methylation, catalyzed by catechol-O-methyltransferase (COMT), inactivates catechol estrogens. COMT is polymorphic in the human population, with 25% of Caucasians being homozygous for a low activity allele of the enzyme (COMT(LL)). We hypothesized that low activity COMT may be a risk factor for human breast cancer and designed a PCR-based RFLP assay to determine COMT genotype in a cohort of 112 matched, nested case-control samples. In the total study population, the odds ratios for the association of breast cancer risk with COMT(HL) and COMT(LL) genotypes were 1.30 [confidence interval (CI), 0.66-2.58] and 1.45 (CI, 0.69-3.07), respectively. Postmenopausal COMT(LL) women had a greater than 2-fold increased risk of developing breast cancer [odds ratio (OR), 2.18; CI, 0.93-5.11]. The association of COMT(LL) with the development of postmenopausal breast cancer was stronger and statistically significant in those women with a body mass index >24.47 kg/m2 (OR, 3.58; CI, 1.07-11.98). When COMT(LL) was combined with either glutathione S-transferase (GST) M1 null or with GSTP1 Ile-105-Val/Val-105-Val (intermediate/low activity, respectively) genotypes, the risk for developing postmenopausal breast cancer was also significantly increased. Our findings suggest that the allele encoding low activity COMT may be an important contributor to the postmenopausal development of breast cancer in certain women.
authors.affiliation: Department of Environmental Health Sciences, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205-2179, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Lavigne
authors.forename: K J
authors.initials: KJ
authors.lastname: Helzlsouer
authors.forename: H Y
authors.initials: HY
authors.lastname: Huang
authors.forename: P T
authors.initials: PT
authors.lastname: Strickland
authors.forename: D A
authors.initials: DA
authors.lastname: Bell
authors.forename: O
authors.initials: O
authors.lastname: Selmin
authors.forename: M A
authors.initials: MA
authors.lastname: Watson
authors.forename: S
authors.initials: S
authors.lastname: Hoffman
authors.forename: G W
authors.initials: GW
authors.lastname: Comstock
authors.forename: J D
authors.initials: JD
authors.lastname: Yager
mesh_terms: D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
chemical_list: D004273:DNA, Neoplasm; D004247:DNA; D002394:Catechol O-Methyltransferase