The Relationship Between Single Nucleotide Polymorphisms In Estrogen-Metabolizing Genes CYP1A1, CYP17, COMT And Estrogen Receptor Alpha Gene And The Risk Of Endometrial Adenocarcinoma

Objective:To examine whether polymorphisms of the genes responsible for catechol estrogen(CE) formation via estrogen biosynthesis (CYP17) and hydroxylation (CYP1A1) and CE inactivation (COMT) and ER α are associated with an elevated risk for endometrial adenocarcinoma in Chinese women.Methods: we conducted a multigenic case-control study ,eighty-seven endometrial adenocarcinoma patients and one hundred and eighty controls were recruited.PCR-RFLP and ASA-PCR assays were used to determine the genotypes of estrogen-metabolizing genes and ER α gene.Result: (1) The endometrial adenocarcinoma risk associated with individual susceptibility genotypes varied among the six polymorphic sites. Ile/Ile, Ile/Val, Val/Val genotype of CYP1A1 Ile/Ile polymorphism site and A1/A1 , A1/A2, A2/A2 of CYP17 MspAI1 polymorphic site has significant difference between the endometrial adenocarcinoma group and control group.(2) CYP17 A1/A1, CYP17A1/A2,CYP1A1 MspI wt/vt, CYP1A1 Ile/Val and ER α XbaI xx genotypes are high-risk genotypes of endometrial adenocarcinoma.(3) After simultaneous consideration of all six genes, the CYP1A1 MspI genotype remained the most significant determinant for endometrial adenocarcinoma development and was associated with a 3.45 fold increase in risk (95% confidence interval, 1.87-6.38). The following genotypes are CYP1A1 Ile-Val genotype,CYP17 genotype and ER α XbaI genotype. Conclusion: The results suggest that CYP1A1 MspI, CYP1A1 Ile-Val, CYP17 MspA1I and ER α XbaI genotypes are related to the susceptibility of endometrial adenocarcinoma. While the allele encoding for low acticity COMT ,ER α PvuIImay not be a genetic risk factor for endometrial adenocarcinoma.