Gene-environment interaction for polymorphisms in ataxia telangiectasia-mutated gene and radiation exposure in carcinogenesis: results from two literature-based meta-analyses of 27120 participants

PURPOSE: We conducted two meta-analyses of ATM genetic polymorphisms and cancer risk in individuals with or without radiation exposure to determine whether there was a joint effect between the ATM gene and radiation exposure in carcinogenesis. RESULTS: rs1801516, which was the only ATM polymorphism investigated by more than 3 studies of radiation exposure, was eligible for the present study. The meta-analysis of 23333 individuals without radiation exposure from 24 studies showed no association between the rs1801516 polymorphism and cancer risk, without heterogeneity across studies. The meta-analysis of 3787 individuals with radiation exposure from 6 studies showed a significant association between the rs1801516 polymorphism and a decreased cancer risk, with heterogeneity across studies. There was a borderline-significant difference between the ORs of the two meta-analyses (P = 0.066), and the difference was significant when only Caucasians were included (P = 0.011). MATERIALS AND METHODS: Publications were identified by searching PubMed, EMBASE, Web of Science, and CNKI databases. Odds ratios (ORs) were calculated to estimate the association between ATM genetic polymorphisms and cancer risk. Tests of interaction were used to compare differences between the ORs of the two meta-analyses. CONCLUSIONS: Our meta-analyses confirmed the presence of a gene-environment interaction between the rs1801516 polymorphism and radiation exposure in carcinogenesis, whereas no association was found between the rs1801516 polymorphism and cancer risk for individuals without radiation exposure. The heterogeneity observed in the meta-analysis of individuals with radiation exposure might be due to gene-ethnicity or gene-gene interactions. Further studies are needed to elucidate sources of the heterogeneity.