Cell proliferation-related genetic polymorphisms and gastric cancer risk: systematic review and meta-analysis

Apart from Helicobacter pylori infection and lifestyle factors, host genetic susceptibility has been suggested to contribute to individual variation in gastric cancer risk as well. Aiming to evaluate the associations between host cell proliferation-related genetic polymorphisms and gastric cancer susceptibility, we reviewed the related studies published until 15 September 2008 and quantitatively summarized the associations of the most widely studied polymorphisms (TP53 Arg72Pro, L-myc EcoRI) using meta-analysis. Fifty-five eligible studies were included in this review. Twenty-three polymorphisms significantly related to gastric cancer risk in at least one study were identified. Polymorphisms determining higher levels of growth factors, which are important for tissue repair, were recently observed to be associated with reduced risk of gastric cancer. In the meta-analysis, TP53 72Pro was associated with increased risk of diffuse gastric cancer among Asians (OR, 1.44; 95% CI, 1.04-1.99), but decreased risk of intestinal gastric cancer among Caucasians (OR, 0.56; 95% CI, 0.36-0.89). This review suggests that cell proliferation-related genetic polymorphisms could be candidate biomarkers of gastric cancer risk, but current evidence for the use for risk stratification is still very limited. Modestly significant associations in meta-analyses stratified by population or type of gastric cancer may be observed by chance because of the limited number of studies and small sample size. Larger studies are warranted to clarify the effect of cell proliferation-related genetic polymorphisms on gastric carcinogenesis.