Common genetic variants on 3q28 contribute to non-small cell lung cancer susceptibility: evidence from 10 case-control studies

The association between common variations (rs10937405, rs4488809) on 3q28 and lung cancer has been widely evaluated in various ethnic groups, since it was first identified through genome-wide association approach. However, the results have been inconclusive. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis. The random-effects model was applied, addressing heterogeneity and publication bias. A total of 10 articles involving 36,221 cases and 58,108 controls were included. Overall, the summary per-allele OR of 1.19 (95 % CI 1.14-1.25, P < 10(-5)) and 1.17 (95 % CI 1.10-1.23, P < 10(-5)) was found for the rs10937405 and rs4488809 polymorphisms, respectively. Significant results were also observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. Significant results were found in East Asians when stratified by ethnicity, whereas no significant associations were found among Caucasians. After stratifying by sample size, study design, control source and sex, significant associations were also obtained. In addition, our data indicate that these polymorphisms are involved in lung cancer susceptibility and confer its effect primarily in lung adenocarcinoma when stratified by histological subtype. Furthermore, significant associations were also detected both never-smokers and smokers for these polymorphisms. In conclusion, this meta-analysis demonstrated that rs10937405 and rs4488809 are a risk factor associated with increased non-small cell lung cancer susceptibility, particularly for East Asian populations.