Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk

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• 作者：Katie A. Ashton ; Anthony Proietto ; Geoffrey Otton ; Ian Symonds ; Mark McEvoy ; John Attia ; Michael Gilbert ; Ute Hamann ; Rodney J. Scott
• 关键词：Estrogen ; Polymorphisms ; Endometrial cancer ; Steroidogenesis ; Estrogen metabolism
• 刊名：Cancer Epidemiology
• 出版年：2010
• 出版时间：June 2010
• 年：2010
• 卷：34
• 期：3
• 页码：328-337
• 全文大小：168 K

文摘

Objectives: The incidence of endometrial cancer has recently increased substantially and studies have shown that altered levels of exogenous and endogenous hormones are associated with individual variation in endometrial cancer risk. The environmental and reproductive risk factors that influence these hormones are well known, however, genetic variants involved in hormone biosynthesis and estrogen metabolism have not been well established in endometrial cancer. Methods: To determine whether polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways are associated with endometrial cancer risk, 28 polymorphisms in 18 genes were genotyped in 191 endometrial cancer cases and 291 healthy controls. Results: The GSTM1 deletion and the variant (GG) genotype of the CYP1B1 rs1800440 polymorphism were associated with a decreased risk of developing endometrial cancer. Furthermore, combinations of haplotypes in CYP1A1, CYP1B1 and GSTs were associated with a decreased risk. The analysis of the repeat polymorphisms revealed that women with the long repeat allele length of the ESR1 (GT)n repeat polymorphism were at an increased risk of developing endometrial cancer. Conversely, women with two long repeat length alleles of the (CAG)n repeat polymorphism in the AR correlated with a decrease in endometrial cancer risk compared to women with one or two alleles with the short repeat length. Conclusions: The findings are consistent with our hypothesis that variability in genes involved in steroidogenesis and estrogen metabolism may alter the risk of developing endometrial cancer, suggesting that they may be useful as biomarkers for genetic susceptibility to endometrial cancer.