EPHX1 polymorphisms and the risk of lung cancer: a HuGE review.
BACKGROUND
Microsomal epoxide hydrolase 1 (EPHX1) plays an important role in both the activation and detoxification of tobacco-derived carcinogens. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to review and summarize the available molecular epidemiologic studies of lung cancer and EPHX1.


METHODS
We searched MEDLINE, Current Contents, and Web of Science databases for studies published before August 2004. We conducted a systematic review and meta-analysis of 13 case-control studies. Summary odds ratios and summary prevalence of the variant allele (genotype) of both polymorphisms in the EPHX1 gene were calculated using the DerSimonian and Laird method.


RESULTS
The low-activity (variant) genotype of EPHX1 polymorphism at exon 3 was associated with decreased risk of lung cancer (odds ratio = 0.65; 95% confidence interval = 0.44-0.96) in lung cancer risk among whites. In white populations, the high-activity (variant) genotype of EPHX1 polymorphism at exon 4 was associated with a modest increase in risk of lung cancer (1.22; 0.79-1.90) and the predicted low activity was associated with a modest decrease in risk (0.72; 0.43-1.22).


CONCLUSIONS
EPHX1 enzyme may act as a phase I enzyme in lung carcinogenesis. The low-activity genotype of EPHX1 gene is associated with decreased risk of lung cancer among whites.
Kiyohara
Chikako
C
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. chikako@phealth.med.kyushu-u.ac.jp
Yoshimasu
Kouichi
K
Takayama
Koichi
K
Nakanishi
Yoichi
Y
D003043:Cocarcinogenesis; D004851:Epoxide Hydrolases / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic; D012307:Risk Factors
D004851:Epoxide Hydrolases