Microsomal epoxide hydrolase polymorphisms and lung cancer risk: a quantitative review.
To investigate the role of microsomal epoxide hydrolase (mEH) polymorphisms in the aetiology of lung cancer and to assess the interaction between mEH polymorphisms and smoking, we performed a meta-analysis of seven published studies, which included 2078 cases and 3081 controls, and a pooled analysis of eight studies (four published and four unpublished at that time) with a total of 986 cases and 1633 controls. The combined meta-analysis odds ratios (ORs) were 0.98 (95% confidence interval [CI] = 0.72-1.35) for polymorphism at amino acid 113 in exon 3 (His/His versus Tyr/Tyr genotype) and 1.00 (95% CI = 0.71-1.41) for polymorphism at amino acid 139 in exon 4 (Arg/Arg versus His/His genotype). In the pooled analysis, we observed a significant decrease in lung cancer risk (OR = 0.70, 95% CI = 0.51-0.96) for exon 3 His/His genotype after adjustment for age, sex, smoking and centre. The protective effect of exon 3 polymorphism seems stronger for adenocarcinoma of the lung than for other histological types. The OR for high predicted mEH activity, compared with low activity, was 1.54 (95% CI = 0.77-3.07) in the meta analysis and 1.18 (95% CI = 0.92-1.52) in the pooled analysis. We did not find a consistent modification of the carcinogenic effect of smoking according to mEH polymorphism, although the risk of lung cancer decreased among never smokers with high mEH activity and among heavy smokers with the exon 3 His/His genotype. In conclusion, this study suggests a possible effect of mEH polymorphisms at exon 3 in modulating lung cancer. If present, this effect may vary among different populations, possibly because of interaction with genetic or environmental factors.
Lee
Won Jin
WJ
International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69008 Lyon, France.
Brennan
Paul
P
Boffetta
Paolo
P
London
Stephanie J
SJ
Benhamou
Simone
S
Rannug
Agneta
A
To-Figueras
Jordi
J
Ingelman-Sundberg
Magnus
M
Shields
Peter
P
Gaspari
Laura
L
Taioli
Emanuela
E
D000328:Adult; D000368:Aged; D016001:Confidence Intervals; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012016:Reference Values; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D004851:Epoxide Hydrolases