Microsomal epoxide hydrolase polymorphisms and risk for advanced colorectal adenoma

Wen Yi Huang*, Nilanjan Chatterjee, Stephen Chanock, Michael Dean, Meredith Yeager, Robert E. Schoen, Li Fang Hou, Sonja I. Berndt, Sunita Yadavalli, Christine C. Johnson, Richard B. Hayes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Cigarette smoking is a risk factor for colorectal adenoma, a precursor of colorectal cancer. Microsomal epoxide hydrolase (EPHX1) metabolizes polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke. Nonsynonymous variants of EPHX1 at Tyr 113His (exon 3) and His 139Arg (exon 4) are associated, respectively, with low ( 113His) and high ( 139Arg) predicted activity. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we evaluated risks for advanced adenoma in relation to cigarette use and these two EPHX1 variants. We compared 772 cases with advanced adenoma (adenoma ≥1 cm or containing high-grade dysplasia or villous, including tubulovillous, elements) of the distal colon (left-sided, descending colon and sigmoid or rectum) to 777 gender- and age-matched controls who were screennegative for left-sided adenoma. Compared to those with homozygous genotypes predicting low EPHX1 activity, advanced adenoma risks tended to be elevated for carriers of 113TyrTyr [odds ratios (OR), 1.5; 95% confidence intervals (CI), 1.0-2.2] and 139ArgArg (OR, 1.4; 95% CI, 0.8-2.5) and for subjects who carried a greater number of the alleles ( 113Tyr or 139Arg) associated with high predicted enzymatic activity (P trend = 0.03). The increased risk associated with the increasing number of putative high-activity alleles was most apparent among current and recent (quit <10 years) cigarette smokers (P trend = 0.02). In conclusion, EPHX1 variants at codon 113 and 139 associated with high predicted enzymatic activity appear to increase risk for colorectal adenoma, particularly among recent and current smokers.

Original languageEnglish (US)
Pages (from-to)152-157
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Issue number1
StatePublished - Jan 2005

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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