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Background  The human 5p15.33 locus contains two well-known genes, the telomerase reverse transcriptase ( TERT ) and cleft lip and palate transmembrane 1-like ( CLPTM1L ) genes, which have been implicated in carcinogenesis. A common sequence variant, rs401681, located in an intronic region of  CLPTM1L , has been reported to be associated with lung cancer risk based on genome-wide association study. However, subsequent replication studies in diverse populations have yielded inconsistent results. In addition, genetic variants at 5p15.33, including rs401681, have been shown to be involved in the susceptibility to multiple malignancies. Nevertheless, the role of these  TERT-CLPTM1L  variants in the etiology of esophageal squamous cell carcinoma (ESCC) remains unknown.    Methods  We genotyped the rs401681 polymorphism using TaqMan methodology and analyzed its association with the risk of lung cancer and ESCC in a case–control study of 1,479 cancer patients (726 with lung cancer and 753 with ESCC) and 860 healthy individuals.    Results  Logistic regression analyses revealed that rs401681 T genotypes were associated with a significantly decreased risk of lung cancer (CT vs. CC: adjusted OR = 0.782, 95% CI = 0.625–0.978,  P  = 0.031; CT/TT vs. CC: adjusted OR = 0.786; 95% CI = 0.635–0.972,  P  = 0.026). Stratification analysis by histology type indicated that rs401681 T genotypes were associated with a significantly reduced risk of both adenocarcinoma and squamous cell carcinoma. Furthermore, no significant association was observed between rs401681 and the risk of ESCC (CT vs. CC: adjusted OR = 0.910, 95% CI = 0.734–1.129,  P  = 0.392; TT vs. CC: adjusted OR = 0.897, 95%CI = 0.624–1.290,  P  = 0.558; CT/TT vs. CC: adjusted OR = 0.908, 95% CI = 0.740–1.114,  P  = 0.355).    Conclusions  Our findings provide further evidence supporting rs401681 as a genetic variant associated with the risk of lung cancer. In addition, we investigated the correlation between the rs401681 variant and the risk of ESCC in a Han Chinese population, and our results suggest that this genetic variant may not be involved in ESCC risk.

Genetic Variant rs401681 at 5p15.33 Modifies Susceptibility to Lung Cancer but Not Esophageal Squamous Cell Carcinoma