Associations of the Insertion/Deletion Polymorphism in the ACE Gene and Risk of Gastric Cancer: A Meta-Analysis.

BACKGROUND

Reported associations of ACE polymorphisms with gastric cancer have been inconsistent, prompting a meta-analysis of 12 published case-control studies where we estimated risk (odds ratio [OR]).

METHODS

We searched MEDLINE through PubMed and EMBASE for suitable articles that had case-control design with gastric cancer as outcome. In this meta-analysis, our overall findings were subjected to modifier analyses (outlier and sensitivity treatments). We also performed subgroup analysis based on ethnicity (German and Japanese) and histological subtype (intestinal and diffuse).

RESULTS

Significance of the protective effects among homozygote carriers of the II genotype (OR 0.54-0.63, P = 0.01-0.02) disappeared with outlier analysis (OR 0.81-0.88, P = 0.12-0.14). Among DD homozygotes, this treatment altered the direction of association from weak protection (OR 0.95-0.96, P = 0.79-0.82) to increased risk (OR 1.13-1.19, P = 0.14-0.16). No significant associations were observed among ID genotype carriers (OR 0.91-0.94, P = 0.69-0.72). Japanese pooled effects varied across the genotype comparisons (OR 0.93-1.06, P = 0.54-0.72). Sensitivity treatment demonstrated robustness of the II genotype, but not the other two, both in overall and subgroup analyses. Histological subtype analysis yielded protection from intestinal cancer across the comparisons (OR 0.38-0.71, P = 0.15-0.50) but variable results for the diffuse type (OR 0.59-1.32, P = 0.19-0.92).

CONCLUSION

In summary, carriers of the ACE II genotype appear to be protected from gastric cancer, regardless of ethnicity or tumor type.