Effect of ATM-111 (G>A) Polymorphism on Cancer Risk: A Meta-Analysis

To assess the relationship between the ataxia telangiectasia mutated (ATM) gene-111 (G>A) polymorphism and cancer risk.

The PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure databases were searched comprehensively. A total of 16 case-control studies with 12,273 cases and 13,046 controls were included in this meta-analysis; 12 of them were from the Chinese population. Five studies assessed smoking effects, including 3038 smokers and 1003 nonsmokers. Odds ratio (OR) was determined by using a genetic model-free approach. Heterogeneity was quantified by I(2) statistics. Publication bias was also evaluated.

The recessive model (AA vs. AG + GG) was suggested as the most appropriate genetic model. After elimination of heterogeneity, it was found that the ATM-111 (G>A) AA genotype is significantly associated with increased susceptibility to overall cancer risk in a fixed effects model (OR = 1.09; 95% CI = 1.03-1.15; p < 0.01; I(2) < 0.01). In the subgroup analysis, the result of pooled analyses among the Chinese population revealed similar associations (OR = 1.12; 95% CI = 1.04-1.22; p < 0.01; I(2) < 0.01). As for specific cancer analysis, an increase was correlated with lung cancer risk (OR = 1.12; 95% CI = 1.01-1.24; p = 0.03) and breast cancer risk (OR = 1.08; 95% CI = 1.00-1.16; p = 0.05). In addition, a stronger association was found among nonsmokers (OR = 1.31; 95% CI = 1.13-1.52; p < 0.01).

This meta-analysis suggests that AA genotype of the ATM-111 gene (G>A) may be a risk factor for breast cancer and lung cancer, especially among nonsmokers, within the Chinese population.