The SNP rs402710 in 5p15.33 Is Associated with Lung Cancer Risk: A Replication Study in Chinese Population and a Meta-Analysis

Xuzai Lu,Xia Luo,Yu Zhang,Lingyan Deng,Zhenling Wang,Yaowu Zhu,Xiaoping Miao,Liming Cheng,Beibei Zhu,Xianxiu Wang,Zhigang Xiong,Wei Chen,Juntao Ke,Huijun Li,Li Zou,Jiao Lou,Ramon Andrade De Mello

doi:10.1371/journal.pone.0076252

Abstract

BackgroundLung cancer is the most commonly diagnosed cancer and leading cause of cancer mortality in the world. A single nucleotide polymorphism (SNP), rs402710, located in 5p15.33, was firstly identified to be associated with the lung cancer risk in a genome-wide association study. However, some following replication studies yielded inconsistent results.Methodology and FindingsA case-control study of 611 cases and 1062 controls in a Chinese population was conducted, and then a meta-analysis integrating the current and previously published studies with a total 31811 cases and 36333 controls was performed to explore the real effect of rs402710 on lung cancer susceptibility. Significant associations between the SNP rs402710 and lung cancer risk were observed in both case-control study and meta-analysis, with ORs equal to 0.77 (95%CI = 0.63–0.95) and 0.83 (95%CI = 0.81–0.86) in dominant model, respectively. By stratified analysis of our case-control study, the associations were also observed in never smoker group and non-small cell lung cancer(NSCLC) group with ORs equal to 0.71 (95%CI = 0.53–0.95) and 0.69 (95%CI = 0.55–0.87), which was remarkable that larger effect of the minor allele T was seen in the two groups than that in overall lung cancer. Besides, the sensitive and cumulative analysis indicated the robust stability of the current results of meta-analysis.ConclusionThe results from our replication study and the meta-analysis provided firm evidence that rs402710 T allele significantly contributed to decreased lung cancer risk, and the case-control study implied that the variant may yield stronger effect on NSCLC and never smokers. However, the mechanism underlying the polymorphism conferring susceptibility to lung cancer is warranted to clarify in the follow-up studies.

Highlights

Lung cancer is the most commonly diagnosed cancer and leading cause of cancer mortality worldwide, with 1.61 million newly confirmed cases and 1.38 million death from lung cancer annually [1].There are multiple factors attributing to lung cancer, of which environmental exposure, primarily to smoking, is the major risk factor
The results from our replication study and the meta-analysis provided firm evidence that rs402710 T allele significantly contributed to decreased lung cancer risk, and the case-control study implied that the variant may yield stronger effect on non-small-cell lung cancer (NSCLC) and never smokers
The mechanism underlying the polymorphism conferring susceptibility to lung cancer is warranted to clarify in the follow-up studies

Summary

Introduction

Lung cancer is the most commonly diagnosed cancer and leading cause of cancer mortality worldwide, with 1.61 million newly confirmed cases and 1.38 million death from lung cancer annually [1].There are multiple factors attributing to lung cancer, of which environmental exposure, primarily to smoking, is the major risk factor. Multiple genome-wide association studies have identified multiple novel SNPs on chromosome 15q25 [8,9,10], 5p15 [11,12] and 6q21 [11], associated with lung cancer Among these SNPs, rs402710 on 5p15.33, located in the intron region of cleft lip and palate transmembrane 1-like (CLPTM1L), was firstly identified in a GWAS set of 3,259 cases and 4,159 controls and a replication set of 2,899 cases and 5,573 controls by McKay JD et al [12]. A single nucleotide polymorphism (SNP), rs402710, located in 5p15.33, was firstly identified to be associated with the lung cancer risk in a genome-wide association study.

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