Irradiation-induced telomerase activity and the risk of lung cancer: a pilot case-control study.
BACKGROUND
Telomerase activity is undetectable in most normal somatic cells, but is up-regulated by various mechanisms during tumorigenesis. Telomerase activation enables cells to overcome replicative senescence and maintain telomere stability during cell proliferation. The aim of the study was to evaluate the association between irradiation-induced telomerase activity and the risk of lung cancer.


METHODS
A case-control design was used that measured the baseline and gamma-radiation-induced telomerase activity in cultured peripheral blood lymphocytes from 44 lung cancer patients and 44 healthy controls. The associations between gamma-radiation-inducible telomerase activity and the risk of lung cancer were then analyzed.


RESULTS
The baseline telomerase activity was lower in cases than in controls (0.956 vs 1.222, P = .126). After gamma-radiation the telomerase activity in cases experienced a significant increase over baseline (1.480 vs 0.956, P < .001); the telomerase activity in controls also increased, but on a smaller scale (1.485 vs 1.222, P = .0025). The relative gamma-radiation-induced telomerase activity, defined as the ratio of the net increase of telomerase activity (gamma-radiation induced minus baseline) to the baseline telomerase activity, was significantly higher in cases than in controls (0.730 vs 0.224, P = .0003). When dichotomized, the subjects at the 75th percentile of the relative gamma-radiation-induced telomerase activity in controls, a higher ratio was associated with a significantly increased lung cancer risk (odds ratio [OR], 4.71, 95% confidence interval [CI]: 1.37, 16.21). Moreover, a dose response was observed between the relative gamma-radiation-induced telomerase activity and lung cancer risk. Compared with individuals with the lowest tertile of the relative gamma-radiation-induced telomerase activity, individuals with the second and the highest tertiles of the relative telomerase activity exhibited significantly elevated risks of lung cancer, with adjusted ORs of 12.58 (95% CI: 1.08, 146.86) and 31.08 (95% CI: 2.71, 356.81), respectively (P for trend <.001).


CONCLUSIONS
The pilot-case control study suggested that the gamma-radiation-induced telomerase activation is associated with a significantly increased risk of developing lung cancer. Larger case-control studies and prospective studies are needed to confirm the findings.
Chen
Meng
M
Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Gu
Jian
J
Xing
Jinliang
J
Spitz
Margaret R
MR
Wu
Xifeng
X
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005720:Gamma Rays; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000453:epidemiology*; D008214:Lymphocytes / Q000201:enzymology / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012306:Risk; D019098:Telomerase / Q000032:analysis* / Q000528:radiation effects*
D019098:Telomerase