Abstract
Microsomal epoxide hydrolase (mEH) gene is polymorphic and its enzyme is involved in the activation and subsequent detoxification of several tobacco carcinogens, for example polycyclic aromatic hydrocarbons. Therefore, we have investigated the association of two polymorphisms at exons 3 and 4 of the mEH gene with the development of lung cancer in 110 patients and 119 matched controls. In addition, we have investigated the relationship between the different mEH alleles and the frequency of chromosome aberrations (CA), as an approach to understand the role of genetic susceptibility on cancer risk. Our results show that only the homozygous exon 4 fast genotype is significantly associated with increased risk for lung cancer (odds ratio [OR] = 6.26; 95% confidence interval [CI] = 1.02-38.3). When the exons 3 and 4 polymorphisms are considered together, patients carrying the high enzyme activity genotype have a significantly increased risk for lung cancer (OR = 2.46; 95% CI = 1.06-5.68). More importantly, the increased risk for this group is confirmed by their having the highest frequency of CA compared to any other genotype groups. In addition, genotypes with higher risk had consistently more CA than those with lower risk. Our CA data also indicates that the low activity genotype may exert a protective role in cigarette smokers, as it was associated with a significant decrease in CA compared to the high and intermediate activity genotypes. In conclusion, the CA data provides evidence to support that susceptibility mEH alleles are significantly involved with the development of lung cancer from cigarette smoking.
| Original language | English |
|---|---|
| Pages (from-to) | 97-102 |
| Number of pages | 6 |
| Journal | Cancer Genetics and Cytogenetics |
| Volume | 145 |
| Issue number | 2 |
| DOIs | |
| State | Published - Sep 2003 |
Bibliographical note
Funding Information:This study was partially supported by a grant from the NIEHS Center Grant (no. ES06676) to the University of Texas Medical Branch (UTMB) and Colciencias-Fulbright-LASPAU fellowships to N.C.S. and to C.H.S.T. The study utilized services from the General Clinical Research Center (GCRC) with funding from the National Center for Research Resources (no. M01 RR-00073), and services from the Molecular Biology Core of the NIEHS Center, both at UTMB. The authors express their appreciation to Dr. David Eastmond from the University of California at Irvine for providing us with the classical probe for the FISH assay, Dr. Andrew Wyrobek and his student Eddy Sloter from the Lawrence Livermore National Laboratory for the technical advice, and the UTMB's staff in the various clinics and offices for their support.
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
