Catechol-O-methyltransferase polymorphism is not associated with ovarian cancer risk

A valine-108-methionine polymorphism in exon 4 of the catechol-O-methyltransferase (COMT) gene causes a 3- to 4-fold reduction in enzyme activity and has been associated with an increased risk of breast cancer. This increased risk may be attributable to a decreased ability of the protein encoded by the low-activity allele (COMT(L)) to methylate and inactivate catechol estrogens, which have been implicated in estrogen carcinogenesis. Because estrogens have also been implicated in the etiology of ovarian cancer, we analyzed 108 cases and 106 controls from a case-control study conducted in Mainz, Germany, to test the hypothesis that COMT(L) is associated with ovarian cancer risk. No significant association was found between the COMT genotype and ovarian cancer risk (for the intermediate-activity COMT genotype versus the high-activity COMT genotype, OR, 1.29; 95% CI, 0.63-2.64; for the low-activity COMT genotype versus the high-activity COMT genotype, OR, 1.17; 95% CI, 0.52-2.61). We also hypothesized that women who were both low-activity COMT genotype- and glutathione S-transferase (GST) M1- and/or T1 null would be at higher risk for ovarian cancer because the combination of these genotypes could theoretically lead to higher catechol estrogen exposure. However, the association between the COMT polymorphism and ovarian cancer risk was similar across GSTM1 and GSTT1 genotypes (Ptrend > 0.40, for all strata). Because of the small sample size of this study population, odds ratios of a small magnitude could not be completely ruled out; however, the results presented do not support a strong association between the COMT polymorphism and the risk of ovarian cancer.