Estrogen receptor alpha gene polymorphisms and risk of prostate cancer: a meta-analysis involving 18 studies

Genetic and epigenetic changes in the estrogen receptor alpha (ER-α) gene, according to multiple lines of evidence, might alter its expression and its downstream signaling thereby increasing the risk of developing prostate cancer. The purpose of this meta-analysis was to determine whether polymorphisms in two intronic restriction sites in the ER-α (PvuII and XbaI) gene contribute to prostate cancer. A literature search for eligible studies published before November 5, 2013 was conducted in the PubMed, Embase, China Biology Medicine (CBM), and CNKI databases. Pooled crude odds ratios (ORs) and their corresponding 95 % confidence intervals (CIs) were calculated. Eighteen case-control and cohort studies were included in this meta-analysis with a total 4,884 prostate cancer cases and 10,134 healthy controls. Two common ER-α polymorphisms were examined: IVS1-397 C>T (a.k.a. the PvuII restriction site, rs2234693) and IVS1-351 A>G (a.k.a. the XbaI restriction site, rs9340799). Results from this meta-analysis showed that the PvuII polymorphism was not significantly associated with prostate cancer risk in any of the racial subgroups, either by allelic or genotypic frequencies. However, this meta-analysis revealed that the G allele in the XbaI polymorphism was associated with a statistically significant increase in the risk of prostate cancer. In a stratified analysis based on ethnicity, the XbaI G allele remained significantly correlated with an increased risk of prostate cancer in Africans; this correlation, however, was not found in Caucasians or Asians. In summary, a positive association correlation was observed between frequencies of the XbaI (A>G) polymorphism and prostate cancer, especially in Africans, but not such correlation was found with regard to the frequency of the PvuII (C>T) polymorphism.