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

Qing Lan, Richard Cawthon, Yutang Gao, Wei Hu, Howard D. Hosgood, Francesco Barone-Adesi, Bu Tian Ji, Bryan Bassig, Wong Ho Chow, Xiaoou Shu, Qiuyin Cai, Yongbin Xiang, Sonja Berndt, Christopher Kim, Stephen Chanock, Wei Zheng, Nathaniel Rothman

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere59230
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 26 2013
Externally publishedYes

Fingerprint

telomeres
Telomere
lung neoplasms
Polymorphism
cohort studies
leukocytes
China
Lung Neoplasms
Leukocytes
Blood
Cohort Studies
Cells
genetic polymorphism
Prospective Studies
Genes
Smoking
Telomerase
RNA-Directed DNA Polymerase
women's health
telomerase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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. / Lan, Qing; Cawthon, Richard; Gao, Yutang; Hu, Wei; Hosgood, Howard D.; Barone-Adesi, Francesco; Ji, Bu Tian; Bassig, Bryan; Chow, Wong Ho; Shu, Xiaoou; Cai, Qiuyin; Xiang, Yongbin; Berndt, Sonja; Kim, Christopher; Chanock, Stephen; Zheng, Wei; Rothman, Nathaniel.

In: PLoS One, Vol. 8, No. 3, e59230, 26.03.2013.

Research output: Contribution to journalArticle

Lan, Q, Cawthon, R, Gao, Y, Hu, W, Hosgood, HD, Barone-Adesi, F, Ji, BT, Bassig, B, Chow, WH, Shu, X, Cai, Q, Xiang, Y, Berndt, S, Kim, C, Chanock, S, Zheng, W & Rothman, N 2013, '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', PLoS One, vol. 8, no. 3, e59230. https://doi.org/10.1371/journal.pone.0059230
Lan, Qing ; Cawthon, Richard ; Gao, Yutang ; Hu, Wei ; Hosgood, Howard D. ; Barone-Adesi, Francesco ; Ji, Bu Tian ; Bassig, Bryan ; Chow, Wong Ho ; Shu, Xiaoou ; Cai, Qiuyin ; Xiang, Yongbin ; Berndt, Sonja ; Kim, Christopher ; Chanock, Stephen ; Zheng, Wei ; Rothman, Nathaniel. / 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. In: PLoS One. 2013 ; Vol. 8, No. 3.
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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.",
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AU - Lan, Qing

AU - Cawthon, Richard

AU - Gao, Yutang

AU - Hu, Wei

AU - Hosgood, Howard D.

AU - Barone-Adesi, Francesco

AU - Ji, Bu Tian

AU - Bassig, Bryan

AU - Chow, Wong Ho

AU - Shu, Xiaoou

AU - Cai, Qiuyin

AU - Xiang, Yongbin

AU - Berndt, Sonja

AU - Kim, Christopher

AU - Chanock, Stephen

AU - Zheng, Wei

AU - Rothman, Nathaniel

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N2 - 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.

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