[Cyclooxygenase 2 genetic variant interacting with tobacco smoking and the risk of lung cancer].

Zhonghua Yu Fang Yi Xue Za Zhi 2013 Aug;47(8):736-40

Department of Cancer Chemotherapy and Radiology, Tangshan Gongren Hospital, Tangshan 063000, China.

Objective: To explore the association of -1195G > A genetic variant in the promoter region of cyclooxygenase 2 genetic (COX2) with the genetic susceptibility of lung cancer and its interaction with smoking.

Methods: Totally, 956 lung cancer patients recruited between January 2000 and December 2008 at Cancer Hospital, Chinese Academy of Medical Science as the case group, and 994 frequency-matched controls were randomly selected from a pool of cancer-free subjects recruited from a nutritional survey. All subjects were ethnic Han Chinese. There was no sex, age restrictions. Case group and control group were matched. Informed consent was obtained and 2 ml peripheral blood was collected from each subject. All samples were genotyped by polymerase chain reaction-restriction fragment length polymorphism method, smoking status of the subjects was surveyed.While the OR and 95% CI were estimated by logistic regression to evaluate the relation of COX2 -1195G > A variant and the risk of lung cancer.

Results: The genetic allele COX2 -1195AA of control group and case group were 24.9% (247/994) and 28.3% (271/956) . Case-control analysis showed an increased risk of developing lung cancer for -1195AA genotype carriers (OR = 1.36, 95% CI: 1.03-1.79), compared with -1195GG carriers. When stratified by smoking status, the significant increased risk of lung cancer was found among smokers with COX2-1195AA genotype, with the OR (95%CI) was 1.56 (1.08-2.25); while among non-smokers, difference of lung cancer risk was not found among different genotypes (OR = 1.17; 95%CI: 0.77-1.61). Among heavy smokers (pack-year >20), -1195AA and -1195AG genotype carriers have significant increased risk of lung cancer with 1.85 (1.16-2.95) and 1.62(1.08-2.43) of OR (95%CI), respectively; among light smokers (pack-year ≤ 20), the OR (95%CI) of lung cancer risk in -1195AG and -1195AA genotype carriers were 0.78 (0.47-1.30) and 1.08 (0.60-1.94), respectively.

Conclusion: Genetic polymorphism in the promoter of COX2 gene interacting with smoking factor plays an important role in the development of lung cancer.

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August 2013
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