Telomere dysfunction: a potential cancer predisposition factor.
BACKGROUND
Genetic instability associated with telomere dysfunction (i.e., short telomeres) is an early event in tumorigenesis. We investigated the association between telomere length and cancer risk in four ongoing case-control studies.


METHODS
All studies had equal numbers of case patients and matched control subjects (92 for head and neck cancer, 135 for bladder cancer, 54 for lung cancer, and 32 for renal cell carcinoma). Telomere length was measured in peripheral blood lymphocytes from study participants. Genetic instability was assessed with the comet assay. Patient and disease characteristics were collected and analyzed for associations with risk for these cancers. All statistical tests were two-sided.


RESULTS
Telomeres were statistically significantly shorter in patients with head and neck cancer (6.5 kilobases [kb]) than in control subjects (7.4 kb) (difference = 0.9 kb, 95% confidence interval [CI] = 0.5 to 1.2 kb; P<.001). Nine percent of patients with head and neck cancer were in the longest quartile of telomere length, whereas 59% were in the shortest quartile. Similar patterns were observed for lung, renal cell, and bladder cancer. When subjects were categorized into telomere length quartiles defined by the distribution in control subjects, the following inverse relationship between telomere length and cancer risk was observed: adjusted odds ratios [ORs] for decreasing quartiles = 0.84 (95% CI = 0.36 to 1.97), 1.77 (95% CI = 0.72 to 4.36), and 5.11 (95% CI = 1.90 to 13.77). In stratified analysis, we found a suggestive greater-than-additive interaction between smoking status and telomere length: for ever smokers with short telomeres, OR = 25.05 (95% CI = 6.91 to 90.73); for never smokers with short telomeres, OR = 6.18 (95% CI = 1.72 to 22.13); and for ever smokers with long telomeres, OR = 6.49 (95% CI = 1.54 to 27.38). Telomere length was statistically significantly and inversely associated with baseline and mutagen-induced genetic instability.


CONCLUSIONS
Short telomeres appear to be associated with increased risks for human bladder, head and neck, lung, and renal cell cancers.
Wu
Xifeng
X
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. xwu@mdanderson.org
Amos
Christopher I
CI
Zhu
Yong
Y
Zhao
Hua
H
Grossman
Barton H
BH
Shay
Jerry W
JW
Luo
Sherry
S
Hong
Waun Ki
WK
Spitz
Margaret R
MR
D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D002292:Carcinoma, Renal Cell / Q000235:genetics; D016022:Case-Control Studies; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics
D004273:DNA, Neoplasm