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


CONCLUSIONS
Genetic polymorphism in the promoter of COX2 gene interacting with smoking factor plays an important role in the development of lung cancer.
Department of Cancer Chemotherapy and Radiology, Tangshan Gongren Hospital, Tangshan 063000, China.
Zhi
Z
Zhang
Rui
R
Liu
Zhao-huan
ZH
Yang
Guang-xia
GX
Wang
Sha-sha
SS
Shao
Qin-qin
QQ
Song
Xue-mei
XM
Zhang
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000009:adverse effects*
D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human