Microsomal epoxide hydrolase polymorphisms and lung cancer risk in non-Hispanic whites

✍ Scribed by Hua Zhao; Margaret R. Spitz; Karin M. Gwyn; Xifeng Wu

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 91 KB
• Volume: 33
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.10023

✦ Synopsis

Abstract

Microsomal epoxide hydrolase (mEPHX) is a critical metabolic enzyme involved in the activation and subsequent detoxification of specific tobacco carcinogens. mEPHX harbors polymorphisms in exon 3 and exon 4 that modulate enzymatic activity. The exon 3 polymorphism decreases mEPHX metabolic activity, whereas the exon 4 polymorphism increases activity. We hypothesized that the mEPHX polymorphisms modulate lung cancer risk. Using a case‐control study design and restriction fragment length polymorphism polymerase chain reaction assay, we determined the mEPHX polymorphic genotypes of 181 lung cancer cases among non‐Hispanic whites and 163 controls (matched for age, sex, ethnicity, and smoking history). Our results showed that the variant allele of mEPHX exon 4 increased the overall lung cancer risk by 56% (odds ratio [OR] = 1.56, 95% confidence interval [CI] = 0.99–2.46). Additionally, the risk estimates were elevated significantly for younger people (< 64 yr) (OR = 2.27, 95% CI = 1.15–4.50) and current smokers (OR = 2.22, 95% CI = 1.06–4.65). The variant allele of mEPHX exon 3 had no effect overall (OR = 0.88, 95% CI = 0.56–1.38), but there was a 53% protective effect (OR = 0.47, 95% CI = 0.22–0.99) in younger people. When we analyzed the exon 3 and exon 4 polymorphisms together, those people with the high enzymatic activity genotype had an elevated lung cancer risk of 1.72 (95% CI = 0.90–3.29). This elevated risk was also evident only in younger people. These findings suggest that these variant alleles of exon 3 and exon 4 of mEPHX modulates lung cancer risk. © 2002 Wiley‐Liss, Inc.