The relationship between single nucleotide polymorphisms in estrogenmetabolizing genes CYP1A1,CYP17,COMT and estrogen receptor alpha and the risk of endometrial adenocarcinoma among the Chinese women

Objective:To explore whether polymorphisms of the genes responsible for catechol estrogen(CE)formation via estrogen biosynthesis(CYP17)and hydroxylation (CYP1A1)and CE inactivation(COMT)and ERa are associated with an elevated risk for en- dometrial adenocarcinoma in Chinese women.Methods:A multigenic case-control study was conducted,eighty-seven endometrial adenocarcinoma patients and ninety controls were recrui- ted.PCR-RFLP assays were used to determine the genotypes of estrogen-metabolizing genes and ERa gene.Results:The endometrial adenocarcinoma risk associated with individual susceptibili- ty genotypes varied among the six polymorphic sites and was the highest for CYP17,followed by CYP1 A1 Ile-Val,CYP1A1 MspI,COMT,ERa XhaI and ERa PvuII.Multivariate logistic regres- sion showed the CYP1A1 MspI genotype was the most significant determinant for endometrial adenocarcinoma development and was associated with a 3.61 fold increase in risk(95% confi- dence interval,1.73～7.55).Furthermore,a trend of increasing risk for developing endometrial adenocarcinoma was found in women harboring higher numbers of high-risk genotypes.Conclu- sion:The CYP1A1,CYP17 and ERa XbaI genotypes are related to the susceptibility of endome- trial adenocarcinoma,they may be useful markers for predicting endometrial adenocarcinoma susceptibility.The allele encoding for low acticity COMT,ERa PvuII may not be a genetic risk factor for endometrial adenocarcinoma.

Objective：To explore whether polymorphisms of the genes responsible for catechol estrogen （CE） formation via estrogen biosynthesis （CYP17） and hydroxylation （CYP1A1） and CE inactivation （COMT） and ERa are associated with an elevated risk for endometrial adenocarcinoma in Chinese women. Methods： A multigenic case-control study was conducted,eighty-seven endometrial adenocarcinoma patients and ninety controls were recruited. PCR-RFLP assays were used to determine the genotypes of estrogen-metabolizing genes and ERa gene. Results：The endometrial adenocarcinoma risk associated with individual susceptibility genotypes varied among the six polymorphic sites and was the highest for CYP17 ,followed by CYP1A1 Ue-Val,CYP1A1 MspI,COMT,ERa XbaI and ERa PvuII. Multivariate logistic regression showed the CYP1A1 MspI genotype was the most significant determinant for endometrial adenocarcinoma development and was associated with a 3.61 fold increase in risk （95% confidence interval, 1.73- 7.55 ）. Furthermore, a trend of increasing risk for developing endometrial adenocarcinoma was found in women harboring higher numbers of high-risk genotypes. Conclusion ：The CYP1A1, CYP17 and ERa XbaI genotypes are related to the susceptibility of endometrial adenocarcinoma, they may be useful markers for predicting endometrial adenocarcinoma susceptibility. The allele encoding for low acticity COMT, ERa PvuII may not be a genetic risk factor for endometrial adenocarcinoma.