An updated meta-analysis on association between angiotensin I-converting enzyme gene insertion/deletion polymorphism and cancer risk.

The Alu repetitive sequence insertion/deletion (I/D, rs4646994) polymorphism in the angiotensin I-converting enzyme (ACE) gene may alter cancer susceptibility, but results of current studies are inconclusive. To derive a more precise estimation of the relationship between the ACE I/D polymorphism and cancer risk, we performed an updated meta-analysis of all eligible studies. All studies published up to July 2013 concerning the association between the ACE I/D polymorphism and cancer risk were identified by systematically searching PubMed, EMBASE, Wanfang, CNKI, and Cqvip databases. The odds ratios (ORs) with 95 % confidence intervals (CIs) were pooled using the fixed/random-effects model in Review Manager 5.1 and STATA 12.0. A total of 46 case-control studies including 7,025 cases and 34,911 controls were identified and evaluated. Overall, we did not observe a direct association between the ACE I/D polymorphism and general cancer risk (DD + DI vs. II OR = 0.95, 95 %CI = 0.84-1.07, P = 0.40). In the subgroup analysis by cancer type, a significant increased susceptibility of prostate cancer was found for variant homozygotes (DD vs. II + ID OR = 2.15, 95 %CI = 1.01-4.55, P = 0.05). Additionally, no significant association was observed in other subgroup analyses according to ethnicity, control source, sample size and quality control of genotyping. In summary, our results suggested that the ACE I/D polymorphism might not be a common risk factor for overall cancer susceptibility, but might contribute to the susceptibility of prostate cancer. More studies with larger sample sizes are required in the future.