Association between the Telomerase Reverse Transcriptase (TERT) rs2736098 Polymorphism and Cancer Risk: Evidence from a Case-Control Study of Non-Small-Cell Lung Cancer and a Meta-Analysis

Haijian Wu,Man Jiang,Cuihong Wang,Naian Qiao,Yang Wang,Shikun Wang,Likuan Hu,Neil A Bhowmick

doi:10.1371/journal.pone.0076372

Haijian Wu, Man Jiang + Show 6 more

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https://doi.org/10.1371/journal.pone.0076372

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Abstract

BackgroundA common genetic variant, telomerase reverse transcriptase (TERT) rs2736098, was recently reported to be associated with lung cancer risk in Caucasians. In addition, many studies have investigated the role of this polymorphism in the etiology of cancer of various organs. Nevertheless, the results of related case-control studies remain inconsistent.MethodsWe hypothesized that the genetic risk variant identified in Caucasians may potentially influence the susceptibility to lung cancer in the Chinese population. To test this hypothesis, a case-control study including 539 non-small-cell lung cancer (NSCLC) cases and 627 cancer-free controls was conducted. Furthermore, to investigate the association between rs2736098 and cancer risk, a meta-analysis based on previously published studies and our case-control study was also performed.ResultsMultivariate logistic regression demonstrated that individuals carrying the A allele or the AA genotype exhibited a significantly elevated risk of NSCLC compared with those carrying the G allele or GG genotype (A vs. G: OR = 1.21, 95% CI = 1.02–1.43, P = 0.028; AA vs. GG: OR = 1.48, 95% CI = 1.05–2.09, P = 0.025). Additionally, this association was stronger among adenocarcinoma cases (AA vs. GG: OR = 1.67, 95% CI = 1.12–2.50, P = 0.013; A vs. G: OR = 1.28, 95% CI = 1.05–1.57, P = 0.016). In the meta-analysis, a borderline significant association between the rs2736098 polymorphism and overall cancer risk was observed (AA vs. GG: OR = 1.25, 95% CI = 1.07–1.46; AA vs. AG+GG: OR = 1.22, 95% CI = 1.06–1.41; additive model: OR = 1.10, 95% CI = 1.02–1.18), and further stratifications demonstrated a moderately increased risk for lung and bladder cancer, Asian ethnicity and hospital-based studies.ConclusionsOur results suggest that the rs2736098 polymorphism may contribute to the risk of lung cancer, especially adenocarcinoma, in the Chinese population. In addition, the current meta-analysis indicates that this genetic variant is only weakly associated with overall cancer risk. However, the rs2736098 polymorphism may affect individual susceptibility to lung and bladder cancer. Further studies are needed to validate our findings.

Highlights

Worldwide, lung cancer was the leading cause of cancer deaths in males and the second leading cause of cancer deaths in females in 2008
The multivariate logistic regression model demonstrated that individuals carrying the A allele or AA genotype exhibited a significantly elevated risk of Non-small-cell lung cancer (NSCLC) compared with those carrying the G allele or GG genotype, after adjusting for age, gender and smoking status (A vs. G: odds ratios (OR) = 1.21, 95% confidence interval (CI) = 1.02–1.43, P = 0.028; AA vs. GG: OR = 1.48, 95% CI = 1.05–2.09, P = 0.025)
When analyzed according to the histological type, the effect of the telomerase reverse transcriptase (TERT) rs2736098 polymorphism on the NSCLC risk was significant for adenocarcinomas (A vs. G: OR = 1.28, 95% CI = 1.05–1.57, P = 0.016; AA vs. GG: OR = 1.67, 95% CI = 1.12–2.50, P = 0.013), but not for squamous cell carcinomas (A vs. G: OR = 1.11, 95% CI = 0.89–1.38, P = 0.363; AA vs. GG: OR = 1.23, 95% CI = 0.78–1.94, P = 0.375; AA+AG vs. GG: OR = 1.12, 95% CI = 0.82–1.52, P = 0.487) ( Table 2)

Summary

Introduction

Lung cancer was the leading cause of cancer deaths in males and the second leading cause of cancer deaths in females in 2008. The geographical and temporal patterns of lung cancer incidence are largely determined by tobacco consumption. Lung cancer rates are increasing in countries such as China and several other countries in Asia and Africa, where the smoking prevalence continues to either increase or show signs of stability [1]. The prognosis of NSCLC patients remains poor [3]. A common genetic variant, telomerase reverse transcriptase (TERT) rs2736098, was recently reported to be associated with lung cancer risk in Caucasians. Many studies have investigated the role of this polymorphism in the etiology of cancer of various organs. The results of related case-control studies remain inconsistent

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