Genetic polymorphisms in the estrogen receptor‐α gene and the risk of endometrial cancer: a meta‐analysis

Abstract

Estrogen receptor-α is a key mediator of the estrogen response in endometrial tissue. The most-studied gene variants are the PvuII and XbaI polymorphisms, which may be associated with altered sensitivity to estrogen. However, studies evaluating the associations between these polymorphisms and endometrial cancer risk have produced controversial conclusions. To explore a more robust estimate of the role of estrogen receptor-α polymorphisms in endometrial carcinogenesis, we searched all published articles indexed in PubMed, Web of Science, EBSCO, Highwire and the CNKI database from 1995 to 2010. Data were independently extracted by two reviewers using a standardized data extraction form. Overall, the meta-analysis included 1944 cases and 3075 controls for PvuII polymorphisms, and 1831 cases and 2875 controls for XbaI polymorphisms. Our results did not show any statistically significant association between endometrial cancer risk and either PvuII or XbaI polymorphisms. However, PvuII polymorphisms, both the CT and the CC genotypes, significantly increased the risk of endometrial cancer in an Asian-Australian population (pooled OR = 1.50, 95%CI 1.09-2.08 and pooled OR = 1.55, 95%CI 1.08-2.22, respectively). The CC genotype significantly decreased the risk of endometrial cancer (pooled odds ratio 0.77, 95% confidence interval 0.64-0.94) in a European population. In contrast, the stratified analysis suggested that the XbaI polymorphism was not significantly associated with endometrial cancer between different populations. This meta-analysis provides evidence that PvuII polymorphisms in the ESR1 gene, which encodes for estrogen receptor-α, could modify the susceptibility to endometrial cancer. However, the genetic effect varied between different geographical regions for unknown reasons.