Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: a report from the female lung cancer consortium in Asia.

Authors:
Mitchell J Machiela Chao Agnes Hsiung Xiao-Ou Shu Wei Jie Seow Zhaoming Wang Keitaro Matsuo Yun-Chul Hong Adeline Seow Chen Wu H Dean Hosgood Kexin Chen Jiu-Cun Wang Wanqing Wen Richard Cawthon Nilanjan Chatterjee Wei Hu Neil E Caporaso Jae Yong Park Chien-Jen Chen Yeul Hong Kim Young Tae Kim Maria Teresa Landi Hongbing Shen Charles Lawrence Laurie Burdett Meredith Yeager I-Shou Chang Tetsuya Mitsudomi Hee Nam Kim Gee-Chen Chang Bryan A Bassig Margaret Tucker Fusheng Wei Zhihua Yin She-Juan An Biyun Qian Victor Ho Fun Lee Daru Lu Jianjun Liu Hyo-Sung Jeon Chin-Fu Hsiao Jae Sook Sung Jin Hee Kim Yu-Tang Gao Ying-Huang Tsai Yoo Jin Jung Huan Guo Zhibin Hu Amy Hutchinson Wen-Chang Wang Robert J Klein Charles C Chung In-Jae Oh Kuan-Yu Chen Sonja I Berndt Wei Wu Jiang Chang Xu-Chao Zhang Ming-Shyan Huang Hong Zheng Junwen Wang Xueying Zhao Yuqing Li Jin Eun Choi Wu-Chou Su Kyong Hwa Park Sook Whan Sung Yuh-Min Chen Li Liu Chang Hyun Kang Lingmin Hu Chung-Hsing Chen William Pao Young-Chul Kim Tsung-Ying Yang Jun Xu Peng Guan Wen Tan Jian Su Chih-Liang Wang Haixin Li Alan Dart Loon Sihoe Zhenhong Zhao Ying Chen Yi Young Choi Jen-Yu Hung Jun Suk Kim Ho-Il Yoon Qiuyin Cai Chien-Chung Lin In Kyu Park Ping Xu Jing Dong Christopher Kim Qincheng He Reury-Perng Perng Takashi Kohno Sun-Seog Kweon Chih-Yi Chen Roel C H Vermeulen Junjie Wu Wei-Yen Lim Kun-Chieh Chen Wong-Ho Chow Bu-Tian Ji John K C Chan Minjie Chu Yao-Jen Li Jun Yokota Jihua Li Hongyan Chen Yong-Bing Xiang Chong-Jen Yu Hideo Kunitoh Guoping Wu Li Jin Yen-Li Lo Kouya Shiraishi Ying-Hsiang Chen Hsien-Chih Lin Tangchun Wu Maria Pik Wong Yi-Long Wu Pan-Chyr Yang Baosen Zhou Min-Ho Shin Joseph F Fraumeni Wei Zheng Dongxin Lin Stephen J Chanock Nathaniel Rothman Qing Lan

Int J Cancer 2015 Jul 29;137(2):311-9. Epub 2014 Dec 29.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.

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Source
http://dx.doi.org/10.1002/ijc.29393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733320PMC

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July 2015
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