The CLPTM1L Variant Rs401681is Associated With Lung Cancer Risk：Evidence From A Case-control Study And A Meta-analysis

Background:Lung cancer is the most commonly diagnosed cancer and leading cause of cancermortality worldwide. Smoking is the most important environmental risk factorattributing to lung cancer. Accumulating evidence showed that80%of lung cancerwas caused by smoking, but only20%of smokers would suffer from lung cancer,suggesting that the genetic factors play an important role in the development of lungcancer. Recently multiple genome-wide association studies (GWAS) have identifiedmultiple novel single nucleotide polymorphisms (SNPs) on chromosome5p15.33associated with the risk of lung cancer. Rs401681located in the intron region of cleftlip and palate transmembrane1-like (CLPTM1L), the association between the lociand lung cancer was firstly identified in2008. However, some replication studies inCaucasian and Asian showed the inconsistent with the association.Objectives:1. To explore the association between the SNP rs401681in CLPTM1L of5p15.33region and the risk of lung cancer in Chinese population.2. To analysis the association between the genetic models of rs401681and risk of lungcancer.Methods:In current study, we performed a hospital-based case–control study of611lungcancer cases and1062age and sex matched cancer-free controls. Candidate polymorphisms rs401681was genotyped by TaqMan PCR method. SPSS19.0wasapplied to analyze the association between genetic variant and lung cancer risk.A meta-analysis combining previously published studies and our current study wasconducted to provide a more precise estimate of the association between CLPTM1Land lung cancer risk. To explain sources of heterogeneity cross studies, stratifiedanalysis, according to ethnicity, study design and tumor subtype, was performed.Sensitivity analysis and cumulative meta-analysis was performed. Publication biaswas detected by funnel plot.Results:The basic information：This study included611lung cancer cases and1062age andsex matched cancer-free controls. The average age of case group was60.97±10.76,and control group was61.71±9.36, with no statistically significant difference(P=0.145). The difference of distribution of smoking status between the two groupswas statistically significant (P＜0.001).Genotype analysis: The significant association between rs401681and decreasedlung cancer was observed in three genetic models (heterozygote model OR=0.79;95%CI=0.64–0.98；dominant model：OR=0.80;95%CI=0.65–0.98；additive model：OR=0.86;95%CI=0.73–0.99).Results of Meta-analysis: The significant association between rs401681anddecreased lung cancer risk was detected in all genetic models（homozygote model：OR=0.78,95%CI=0.67-0.90; heterozygote model: OR=0.86,95%CI=0.81-0.92;dominant model： OR=0.84,95%CI=0.80-0.89; additive model： OR=0.87,95%CI=0.84-0.91）. By stratified analysis, we revealed that ethnicity and study designmight constitute the source of between-study heterogeneity. Besides, the sensitive andcumulative analysis indicated the highly stability of the current results.Conclusions:Our replication study in a Chinese population and the subsequent meta-analysiscollectively confirm genetic involvement of rs401681polymorphism in lung cancer susceptibility.