A genome-wide association study revealed that a single nucleotide polymorphism, CLPTM1L - rs401681 (G>A), located at the 5p15.33 locus was significantly associated with increased risk of various cancers; however, its association with lung cancer is currently inconclusive. In order to explore the relationship between this polymorphism and lung cancer risk more precisely, we performed a meta-analysis of eight eligible studies involving 9935 cases and 11,261 controls. The pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixed- or random-effect models. Results indicated that this polymorphism was significantly associated with lung cancer risk in all genetic models (GA vs GG: OR = 0.88, 95%CI = 0.83-0.94; AA vs GG: OR = 0.81, 95%CI = 0.70-0.93; AA/GA vs GG: OR = 0.86, 95%CI = 0.81-0.91; AA vs
Ga/gg: OR = 0.86, 95%CI = 0.76-0.99). An analysis stratified by ethnicity and source of controls revealed a significantly decreased risk among European groups and population-based studies in all genetic models, and among Asian populations only in the dominant model comparison. Additionally, in a subgroup analysis by histology type, the CLPTM1L rs401681 polymorphism was found to significantly decrease the risks of both adenocarcinoma and squamous cell carcinoma of the lung in all genetic models. In conclusion, our study indicated that the CLPTM1L - rs401681 (G>A) polymorphism was significantly associated with decreased lung cancer risk, especially among European populations. Due to some minor limitations, our findings should be confirmed in further studies.