Objective Lung cancer is the most common cause of cancer deaths worldwide; it is a complex disease that many genes involved (involves many genes) on chromosomes. Recently, several genome wide association studies have identified chromosomal region 15q24-25.1 as a hotspot for lung cancer risk. We therefore aimed to explore the association of CHRNA3 gene rs1051730 and rs8034191 polymorphisms of this region with lung cancer via meta-analysis.

Methods Random-effects model was performed irrespective of the between-study heterogeneity. Data and study quality were assessed in duplicate. Publication bias was evaluated using the fail-safe number.

Results Overall, five studies involving nine populations were identified for both rs1051730 (cases/controls: 7394/8784) and rs8034191 (9553/7953) polymorphisms. Genotype frequencies of two polymorphisms satisfied the Hardy–Weinberg law in controls. Presence of rs1051730 A allele was significantly associated with 32% increased risk of lung cancer (95% CI 1.25 to 1.39; p<0.00001). Contrastingly, rs8034191 C allele only conferred a marginal association yielding 18% increased risk (95% CI 0.99 to 1.42; p=0.07). Under assumption of dominant and recessive modes, risk magnitude was strengthened for rs1051730 with an increased risk of 39% (95% CI 1.30 to 1.48; p<0.00001) and 48% (95% CI 1.25 to 1.76; p<0.00001) for lung cancer, respectively. As for rs8034191, there was marginal or null association for the dominant (pooled OR=1.23; p=0.06) and recessive (pooled OR=1.26; p=0.15) modes. The fail-safe number at the level of 0.05 supported these significant associations.

Conclusions Our results demonstrated that the rs1051730 A allele was significantly associated with an increased lung cancer risk and the effect of rs8034191 polymorphism was moderate.