Estrogen production and metabolism play critical roles in the development and pathogenesis of
endometrial carcinoma.
Cytochrome P450 1B1 (CYP1B1) and
catechol-O-methyltransferase (COMT) are two key
enzymes in the
estrogen metabolism pathway that result in the hydroxylation and conjugation of
estradiol, respectively. We evaluated the association between the CYP1B1 Leu432Val and CYP1B1 Asn453Ser polymorphisms and the COMT Val158Met polymorphism and invasive
endometrial cancer risk in a case-control study nested within the Nurses' Health Study (n = 222 cases, 666 controls). We also evaluated whether body mass index (BMI), postmenopausal
hormone (PMH) use and cigarette smoking modified the associations of the CYP1B1 and COMT genotypes and
endometrial cancer risk. Conditional logistic regression was used to calculate the adjusted odds ratios (OR) and 95% confidence intervals (CI) to quantify the risk of
endometrial cancer among subjects who had at least one variant allele compared with subjects who were homozygous for the wild-type allele. Carriers of the CYP1B1 Ser allele had a statistically significant decreased risk of
endometrial cancer (OR = 0.62; 95% CI, 0.42-0.91); there was no significant association between the CYP1B1 Val allele and
endometrial cancer risk (OR = 1.10; 95% CI, 0.75-1.59). Compared with the COMT
Val/Val wildtype genotype, the adjusted OR of
endometrial cancer for women with the COMT Val/Met or COMT
Met/Met genotype was 0.96 (95% CI, 0.65-1.43). We did not observe any effect modification by BMI, PMH use and cigarette smoking for the CYP1B1 and COMT genotypes. Our data suggest, that the CYP1B1 Ser allele may decrease
endometrial cancer risk by altering the production of
catechol estrogens. However, further studies are warranted to elucidate the role of CYP1B1 in
endometrial cancer.