Journal Article

Mendelian randomization study of telomere length and lung cancer risk in East Asian population

Hu, Zhibin, Ma, Hongxia, Xu, Lin, Fang, Rui, Ma, Zijian, Shen, Hongbing, Jin, Guangfu, Zhu, Meng, Dai, Juncheng, Jiang, Tao, Huang, Mingtao, Cao, Xuguang, Du, Jiangbo

2019

Overview

Associations between telomere length and cancer risk have been investigated in many epidemiological studies, but the results are controversial. These associations may be biased by reverse causation or confounded by environmental exposures. To avoid potential biases, we used Mendelian randomization method to evaluate whether TL is the causal risk factor for lung cancer. We conducted Mendelian randomization analysis in two published East Asian GWAS studies (7127 cases and 6818 controls). We used both weighted genetic risk score and inverse‐variance weighting method to estimate the relationship between TL and lung cancer risk. Nonlinear test also used to detect potential association trends. We observed that increased weight GRS was associated with increased risk of lung cancer (OR = 2.25, 95%CI: 1.81‐2.78, P = 1.18 × 10−13). In different subtypes, weight GRS was significantly associated with lung adenocarcinoma risk (OR = 2.69, 95% CI: 2.11‐3.42, P = 7.20 × 10−16); while lung squamous cell carcinoma showed a marginal association (OR = 1.45, 95% CI = 1.01‐2.10, P = .047). Nonlinear analysis suggested a log‐linear dose‐response relationship between increased weight GRS and lung cancer risk. Our results indicated that longer TL increases lung cancer risk. Those biological mechanisms changes caused by long TL may play an important role in lung carcinogenesis. Telomere length GRS indicated that longer TL increases LC risk. A log linear dose‐response relationship was observed between increased GRS and LC risk.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Adenocarcinoma / Adenocarcinoma of Lung - epidemiology / Adenocarcinoma of Lung - genetics / Apoptosis / Asian Continental Ancestry Group - genetics / Asian population / Bias / Cancer Prevention / Carcinogenesis / Carcinoma, Squamous Cell - epidemiology / Carcinoma, Squamous Cell - genetics / Case-Control Studies / Cell division / Cell growth / Epidemiology / Far East - epidemiology / Genetic Predisposition to Disease / Genome-Wide Association Study / Genomes / Health care / Health risk assessment / Higher education / Humans / Lung cancer / Lung carcinoma / Lung Neoplasms - epidemiology / Lung Neoplasms - genetics / mendelian randomization / Mendelian Randomization Analysis / Mutation / Odds Ratio / Original Research / Polymorphism, Single Nucleotide / Population / Quality control / Risk Factors / Senescence / Smoking / Software / Squamous cell carcinoma / Studies / Telomerase / Telomere - metabolism / Telomere Homeostasis - genetics / telomere length / Variables