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G enetic 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
Author(s) -
Machiela Mitchell J.,
Hsiung Chao Agnes,
Shu XiaoOu,
Seow Wei Jie,
Wang Zhaoming,
Matsuo Keitaro,
Hong YunChul,
Seow Adeline,
Wu Chen,
Hosgood H. Dean,
Chen Kexin,
Wang JiuCun,
Wen Wanqing,
Cawthon Richard,
Chatterjee Nilanjan,
Hu Wei,
Caporaso Neil E.,
Park Jae Yong,
Chen ChienJen,
Kim Yeul Hong,
Kim Young Tae,
Landi Maria Teresa,
Shen Hongbing,
Lawrence Charles,
Burdett Laurie,
Yeager Meredith,
Chang IShou,
Mitsudomi Tetsuya,
Kim Hee Nam,
Chang GeeChen,
Bassig Bryan A.,
Tucker Margaret,
Wei Fusheng,
Yin Zhihua,
An SheJuan,
Qian Biyun,
Lee Victor Ho Fun,
Lu Daru,
Liu Jianjun,
Jeon HyoSung,
Hsiao ChinFu,
Sung Jae Sook,
Kim Jin Hee,
Gao YuTang,
Tsai YingHuang,
Jung Yoo Jin,
Guo Huan,
Hu Zhibin,
Hutchinson Amy,
Wang WenChang,
Klein Robert J.,
Chung Charles C.,
Oh InJae,
Chen KuanYu,
Berndt Sonja I.,
Wu Wei,
Chang Jiang,
Zhang XuChao,
Huang MingShyan,
Zheng Hong,
Wang Junwen,
Zhao Xueying,
Li Yuqing,
Choi Jin Eun,
Su WuChou,
Park Kyong Hwa,
Sung Sook Whan,
Chen YuhMin,
Liu Li,
Kang Chang Hyun,
Hu Lingmin,
Chen ChungHsing,
Pao William,
Kim YoungChul,
Yang TsungYing,
Xu Jun,
Guan Peng,
Tan Wen,
Su Jian,
Wang ChihLiang,
Li Haixin,
Sihoe Alan Dart Loon,
Zhao Zhenhong,
Chen Ying,
Choi Yi Young,
Hung JenYu,
Kim Jun Suk,
Yoon HoIl,
Cai Qiuyin,
Lin ChienChung,
Park In Kyu,
Xu Ping,
Dong Jing,
Kim Christopher,
He Qincheng,
Perng ReuryPerng,
Kohno Takashi,
Kweon SunSeog,
Chen ChihYi,
Vermeulen Roel C.H,
Wu Junjie,
Lim WeiYen,
Chen KunChieh,
Chow WongHo,
Ji BuTian,
Chan John K. C.,
Chu Minjie,
Li YaoJen,
Yokota Jun,
Li Jihua,
Chen Hongyan,
Xiang YongBing,
Yu ChongJen,
Kunitoh Hideo,
Wu Guoping,
Jin Li,
Lo YenLi,
Shiraishi Kouya,
Chen YingHsiang,
Lin HsienChih,
Wu Tangchun,
Wong Maria Pik,
Wu YiLong,
Yang PanChyr,
Zhou Baosen,
Shin MinHo,
Fraumeni Joseph F.,
Zheng Wei,
Lin Dongxin,
Chanock Stephen J.,
Rothman Nathaniel,
Lan Qing
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29393
Subject(s) - telomere , lung cancer , prospective cohort study , cancer , oncology , medicine , population , biology , genetics , gene , environmental health
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.