The CYP19A1 (TTTA)n Repeat Polymorphism, but not Arg264Cys Polymorphism, May Affect the Risk of Prostate Cancer: Evidence from a Meta-Analysis

Abstract Background: Abnormal aromatase (CYP19A1) expression has been proposed to take part in the carcinogenesis of prostate cancer (PCa). However, results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting.This meta-analysis aimed to systematically evaluate the association between the CYP19A1 Arg264Cys polymorphism and (TTTA)n repeat polymorphism and PCa.Methods: Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of association between the CYP19A1 Arg264Cys polymorphism and PCa was assessed by pooled odds ratio (OR) and 95% confidence interval (95% CI) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we took sequentially the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95%CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Results: Pooled estimates of nine eligible studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with the risk of PCa in the overall population and in the Caucasian and Asian subgroups. A meta-analysis of seven studies addressing the (TTTA)n repeat polymorphism revealed that the 8-repeat allele increased PCa risk in the overall population (OR=1.34, 95% CI=1.14–1.58, P=0.001) and in the subgroup with population-based (PB) controls (OR=1.41, 95% CI=1.13–1.74, P=0.002). Although the 7-repeat allele appeared not to affect PCa risk in the overall population, it protected against PCa in the subgroup with PB controls (OR=0.81, 95% CI=0.67–0.98, P=0.03).Conclusions: The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism may affect PCa risk.