Carcinogenesis Advance Access published online on February 26, 2004
Carcinogenesis, doi:10.1093/carcin/bgh126
© 2004 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Department of Epidemiology, Harvard School of Public Health, Boston MA 02115; Harvard Center for Cancer Prevention, Harvard School of Public Health, Boston MA 02115
* Corresponding author. E-mail: gtranah{at}hsph.harvard.edu.
Received 20 November 2003
; revised 22 January 2004
; accepted 14 February 2004
Microsomal epoxide hydrolase (mEH) is involved the bioactivation and detoxification of polycyclic aromatic hydrocarbons derived from tobacco smoke and charred meat intake. Two coding-region mEH variants located in exon 3 (Tyr113His) and exon 4 (His139Arg) have been described and may affect the enzyme's specific activity. We investigated these polymorphisms and tested interactions with smoking and charred meat intake in relation to risk of colorectal adenoma in two case-control studies nested in the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) cohorts. mEH exon 3 and exon 4 polymorphisms were not associated with overall risk of adenoma among 556 incident cases and 557 controls from the NHS or 376 prevalent cases and 725 controls from the HPFS. A statistically significant interaction was found between the exon 4 polymorphism and smoking for in men (P = 0.03) and a borderline significant interaction was found between the exon 3 polymorphism and smoking for in women (P = 0.06). Women having the exon 3 ‘rapid’ Tyr/Tyr genotype were at increased risk when exposed to either
Epoxide hydrolase polymorphisms, cigarette smoking, and risk of colorectal adenoma in the Nurses' Health Study and the Health Professionals Follow-Up Study
2 Department of Epidemiology, Harvard School of Public Health, Boston MA 02115; Department of Nutrition, Harvard School of Public Health, Boston MA 02115; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston MA 02115
3 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston MA 02115
4 Department of Epidemiology, Harvard School of Public Health, Boston MA 02115; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston MA 02115
5 Department of Epidemiology, Harvard School of Public Health, Boston MA 02115; Harvard Center for Cancer Prevention, Harvard School of Public Health, Boston MA 02115; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston MA 02115
25 pack-years smoking [relative risk (RR) = 2.43, 95% confidence interval (CI) 1.47-4.01] or <25 pack-years of smoking (RR = 1.73, 95% CI 1.10-2.73) relative to nonsmokers. Men with the exon 4 ‘slow’ His/His genotype were at increased risk when exposed to 25 pack-years smoking (RR = 2.21, 95% CI 1.43, 3.41) or <25 pack-years smoking (RR = 1.71, 95% CI 1.13-2.59) relative to nonsmokers. Charred meat intake was not associated with adenoma risk and there was no significant interaction with either mEH polymorphism. Our results indicate that individuals exposed to 25 pack-years smoking were at increased risk for colorectal adenoma and that risk is related to dose of tobacco carcinogens and mEH activity level, but the results were not consistent between men and women.
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