OBJECTIVETo explore the prevalence of Val158Met polymorphism in Catechol-O-methyltransferase (COMT) gene and its effect on genetic susceptibility for breast cancer in Shanghai population.

METHODSA total of 114 patients with BRCA1/BRCA 2 negative hereditary breast cancer from independent families and 121 age-matched healthy controls were analyzed. Genotype analysis was conducted by polymerase chain reaction (PCR) and then DNA direct sequencing. The odd ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression model.

RESULTSThe frequency of Val158Met polymorphism GG, GA and AA genotype in case group and control was 0.58 (65), 0.32 (36), 0.10 (11) and 0.60 (66), 0.35 (41), 0.03 (3), respectively. The frequency of allele-containing genotypes is significantly higher in early-onset breast cancer patients (0.57) than in familial ones (0.35). Compared with GG (Val/Val) genotype, AA (Met/Met) genotype confers a significantly increased risk for breast cancer (adjusted OR = 3.15; 95% CI, 0.70 - 14.19), especially among premenopausal women (adjusted OR = 9.98; 95% CI, 1.00 - 99.64). Borderline significantly association was found between AA genotype (adjusted OR = 7.57; 95% CI, 0.57 - 101.28) and susceptibility for breast cancer in BMI < or = 23 kg/m(2) group.

CONCLUSIONSVal158Met polymorphism in COMT gene could be a candidate for low penetrance breast cancer susceptibility in Shanghai population, especially among premenopausal women and early-onset breast cancer patients.