title: Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.
abstract: A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA. qingl@mail.nih.gov
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Richard
authors.initials: R
authors.lastname: Cawthon
authors.forename: Yutang
authors.initials: Y
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: H Dean
authors.initials: HD
authors.lastname: Hosgood
authors.forename: Francesco
authors.initials: F
authors.lastname: Barone-Adesi
authors.forename: Bu-Tian
authors.initials: BT
authors.lastname: Ji
authors.forename: Bryan
authors.initials: B
authors.lastname: Bassig
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Shu
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Xiang
authors.forename: Sonja
authors.initials: S
authors.lastname: Berndt
authors.forename: Christopher
authors.initials: C
authors.lastname: Kim
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002681:China; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000737:chemistry*; D059505:Telomere Homeostasis
chemical_list: C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase
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