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The early genome-wide association studies (GWAS) found a significant association between lung cancer and rs1051730 (15q25) polymorphism. However, the subsequent studies reported consistent and inconsistent results in different populations. Three meta-analysis studies were thus performed to reevaluate the association. But their results remain inconsistent. After that, some new GWAS studies reported conflicting results again. We think that the divergence of these results may be due to small-scale samples or heterogeneity among different populations. Therefore, we reevaluated the association by collecting more samples (N = 33,617 cases and 116,639 controls) from 31 studies, which incorporate 8 new studies and 23 previous studies used by one or more of the three meta-analysis studies. We observed a significant association between lung cancer and rs1051730 in pooled population by using allele (OR = 1.30, 95% CI = 1.27–1.34, P  <  0.0001), dominant (OR = 1.41, 95% CI = 1.29–1.55, P < 0.0001), recessive (OR = 1.53, 95% CI = 1.42–1.65, P < 0.0001) and additive (OR = 1.75, 95% CI = 1.61–1.90, P < 0.0001) models. Through the subgroup analysis, we observed a significant heterogeneity only in East Asian population (P = 0.006, I 2  = 66.9%), and the association is significant in all subgroups (OR = 1.2976, 95% CI = 1.2622–1.3339 (European ancestry), OR = 1.5025, 95% CI = 1.2465–1.8110 (African), OR = 1.7818, 95% CI = 1.3915–2.2815 (East Asian), P < 0.0001). We believe that these results will contribute to understanding the genetic mechanism of lung cancer.

Analyzing large-scale samples confirms the association between the rs1051730 polymorphism and lung cancer susceptibility