Abstract
BackgroundThe 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.MethodsWe 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.ResultsLogistic 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).ConclusionsOur 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.
Highlights
Lung cancer has been the most common cancer in the world for several decades as well as the most common cause of death from cancer
Genome-wide association studies (GWASs) have shown that common telomerase reverse transcriptase (TERT)-cleft lip and palate transmembrane 1-like (CLPTM1L) variants at 5p15.33 may influence the risk of developing lung cancer as well as other types of cancer [5,6,7,8,9,10,11]
Telomeres are the protein-bound DNA repeat structures at the ends of chromosomes and are important in maintaining genomic stability [13,14,15]. Another potential candidate causal gene in the 5p15.33 region is CLPTM1L, which has been reported to be involved in the cellular response to genotoxic stress and cisplatin resistance [16]
Summary
Lung cancer has been the most common cancer in the world for several decades as well as the most common cause of death from cancer. By pooling the available GWAS data on lung cancer, Timofeeva et al [12] identified common susceptibility loci at 5p15 and demonstrated histology-specific effects of 5p15 loci. Both TERT and CLPTM1L are attractive candidate genes, as they have both been implicated in carcinogenesis. Telomeres are the protein-bound DNA repeat structures at the ends of chromosomes and are important in maintaining genomic stability [13,14,15] Another potential candidate causal gene in the 5p15.33 region is CLPTM1L, which has been reported to be involved in the cellular response to genotoxic stress and cisplatin resistance [16]. The role of these TERT-CLPTM1L variants in the etiology of esophageal squamous cell carcinoma (ESCC) remains unknown
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