The relationship between angiotensin-converting enzyme gene insertion/deletion polymorphism and digestive cancer risk: Insights from a meta-analysis

Background and objective: The gene encoding angiotensin-converting enzyme (ACE) has been implicated in the development of several malignancies. We aimed to meta-analyze the association of ACE gene insertion/deletion (I/D) polymorphism with digestive cancer risk and seek possible sources of between-study heterogeneity. Methods: Two authors independently assessed eligibility of each retrieved publication and gathered relevant data. Risk estimates were expressed as odds ratio (OR) and 95% confidence interval (CI). Results: Sixteen publications were qualified for analysis, involving 2903 digestive cancer cases and 10,833 controls. Overall analyses failed to show any significance for digestive cancer risk. There was moderate heterogeneity and lower publication bias for overall comparisons. In subgroup analyses, ACE gene II genotype was associated with a 15% reduced risk (OR=0.85, 95% CI: 0.57-1.27, p=0.434) for gastric cancer, but a 16% increased risk (OR=1.16, 95% CI: 0.89-1.52, p=0.273) for colorectal cancer. By source of controls, the I allele appeared to be a protective factor against digestive cancer in population-based studies (OR=0.87, 95% CI: 0.75-1.00, p=0.055) but a risk-conferring factor in hospital-based studies (OR=1.17, 95% CI: 1.01-1.35, p=0.033). Conclusion: Our findings suggested that ACE gene I allele might be a protective factor against gastric cancer, necessitating further confirmation in large, population-based studies.