Association between environmental tobacco smoke exposure and lung cancer susceptibility: modification by antioxidant enzyme genetic polymorphisms.
BACKGROUND
Environmental tobacco smoke (ETS) is the primary etiologic factor responsible for lung cancer. However, only 10-15 % of smokers develop lung cancer, suggesting a genetic role in modifying individual susceptibility to lung cancer. Antioxidant enzymes and genetic polymorphisms should be considered.


OBJECTIVE
The present study aimed to evaluate the role of antioxidant enzyme activity and genetic polymorphisms in modifying the susceptibility to lung cancer among individuals exposed to ETS.


METHODS
A total of 150 male subjects were divided into three groups: 50 lung cancer patients, 50 chronic smokers, and 50 passive smokers. Genotyping of microsomal epoxide hydrolase (mEH) exon 3 (Tyr(113)Hist) and exon 4 (Hist(139)Arg) polymorphisms were done by the polymerase chain reaction-restriction fragment length polymorphism technique. MnSOD (Val(16)Ala) polymorphism was detected by the real time-TaqMan assay. Erythrocyte MnSOD activity was measured spectrophotometrically.


RESULTS
ETS-exposed individuals (both active and passive smokers) who carried the His allele of mEH exon3 have a 2.9-fold increased risk of lung cancer (odds ratio [OR] 2.9, P < 0.001). In addition, ETS-exposed carriers of the Arg allele of mEH exon 4 have a 2.1-fold increased risk of lung cancer (OR 2.1, P = 0.024). However, no association between the MnSOD Val(16)Ala polymorphism and lung cancer was detected among ETS-exposed individuals (OR 1.6, P = 0.147), although the lung cancer group had significantly lower MnSOD activity than the chronic or passive smoker groups (P = 0.03).


CONCLUSIONS
Exons 3 and 4 polymorphisms of the mEH gene may contribute to lung cancer susceptibility through disturbed antioxidant balance. However, this was not the case with the MnSOD Val(16)Ala single-nucleotid polymorphism. Antioxidant enzymes may modulate the influence of ETS exposure on lung cancer risk.
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt, muna_fathy@hotmail.com.
Mona
M
Fathy
Mai
M
Hamed
Omnia
O
Youssif
Nahla
N
Fawzy
Wafa
W
Ashour
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D014028:Tobacco Smoke Pollution; D013482:Superoxide Dismutase; D004851:Epoxide Hydrolases