Telomere length in white blood cell DNA and lung cancer: a pooled analysis of three prospective cohorts.
We investigated the relationship between telomere length and lung cancer in a pooled analysis from three prospective cohort studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and women in the United States, and previously published data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted among male smokers in Finland, and the Shanghai Women's Health Study (SWHS), which is comprised primarily of never-smokers. The pooled population included 847 cases and 847 controls matched by study, age, and sex. Leukocyte telomere length was measured by a monochrome multiplex qPCR assay. We used conditional logistic regression models to calculate ORs and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk, adjusted for age and pack-years of smoking. Longer telomere length was associated with increased lung cancer risk in the pooled analysis [OR (95% CI) by quartile: 1.00; 1.24 (0.90-1.71); 1.27 (0.91-1.78); and 1.86 (1.33-2.62); P trend = 0.000022]. Findings were consistent across the three cohorts and strongest for subjects with very long telomere length, i.e., lung cancer risks for telomere length [OR (95% CI)] in the upper half of the fourth quartile were 2.41 (1.28-4.52), 2.16 (1.11-4.23), and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS, respectively. In addition, the association persisted among cases diagnosed more than 6 years after blood collection and was particularly evident for female adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker of future increased risk of lung cancer in diverse populations.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland; weijie.seow2@nih.gov.
Wei Jie
WJ
Seow
Department of Human Genetics, University of Utah, Salt Lake City, Utah;
Richard M
RM
Cawthon
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Mark P
MP
Purdue
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Wei
W
Hu
Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine;
Yu-Tang
YT
Gao
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Wen-Yi
WY
Huang
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Stephanie J
SJ
Weinstein
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Bu-Tian
BT
Ji
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
Jarmo
J
Virtamo
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York;
H Dean
HD
Hosgood
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Bryan A
BA
Bassig
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
Xiao-Ou
XO
Shu
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
Qiuyin
Q
Cai
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China; and.
Yong-Bing
YB
Xiang
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Shen
S
Min
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas;
Wong-Ho
WH
Chow
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Sonja I
SI
Berndt
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Christopher
C
Kim
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii;
Unhee
U
Lim
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Demetrius
D
Albanes
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Neil E
NE
Caporaso
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Stephen
S
Chanock
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee;
Wei
W
Zheng
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Nathaniel
N
Rothman
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Qing
Q
Lan
D016022:Case-Control Studies; D015331:Cohort Studies; D004247:DNA / Q000097:blood* / Q000235:genetics; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000648:ultrastructure*; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D016615:Telomere / Q000235:genetics*
D004273:DNA, Neoplasm; D004247:DNA