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Title: 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: Machiela MJ,  Hsiung CA,  Shu XO,  Seow WJ,  Wang Z,  Matsuo K,  Hong YC,  Seow A,  Wu C,  Hosgood HD 3rd,  Chen K,  Wang JC,  Wen W,  Cawthon R,  Chatterjee N,  Hu W,  Caporaso NE,  Park JY,  Chen CJ,  Kim YH,  Kim YT,  Landi MT,  Shen H,  Lawrence C,  Burdett L,  Yeager M,  Chang IS,  Mitsudomi T,  Kim HN,  Chang GC,  Bassig BA,  Tucker M,  Wei F,  Yin Z,  An SJ,  Qian B,  Lee VH,  Lu D,  Liu J,  Jeon HS,  Hsiao CF,  Sung JS,  Kim JH,  Gao YT,  Tsai YH,  Jung YJ,  Guo H,  Hu Z,  Hutchinson A,  Wang WC,  Klein RJ,  Chung CC,  Oh IJ,  Chen KY,  Berndt SI,  Wu W,  Chang J,  Zhang XC,  Huang MS,  Zheng H,  Wang J,  Zhao X,  Li Y,  Choi JE,  Su WC,  Park KH,  Sung SW,  Chen YM,  Liu L,  Kang CH,  Hu L,  Chen CH,  Pao W,  Kim YC,  Yang TY,  Xu J,  Guan P,  Tan W,  Su J,  Wang CL,  Li H,  Sihoe AD,  Zhao Z,  Chen Y,  Choi YY,  Hung JY,  Kim JS,  Yoon HI,  Cai Q,  Lin CC,  Park IK,  Xu P,  Dong J,  Kim C,  He Q,  Perng RP,  Kohno T,  Kweon SS,  Chen CY,  Vermeulen RC,  Wu J,  Lim WY,  Chen KC,  Chow WH,  Ji BT,  Chan JK,  Chu M,  Li YJ,  Yokota J,  Li J,  Chen H,  Xiang YB,  Yu CJ,  Kunitoh H,  Wu G,  Jin L,  Lo YL,  Shiraishi K,  Chen YH,  Lin HC,  Wu T,  Wong MP,  Wu YL,  Yang PC,  Zhou B,  Shin MH,  Fraumeni JF Jr,  Zheng W,  Lin D,  Chanock SJ,  Rothman N,  Lan Q
Journal: Int J Cancer
Date: 2015 Jul 15
Branches: BB, CGR, GEB, HGP, LGS, LTG, OD, OEEB
PubMed ID: 25516442
PMC ID: not available
Abstract: 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.