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Microsomal epoxide hydrolase polymorphisms and risk for advanced colorectal adenoma

  1. Author:
    Huang, W. Y.
    Chatterjee, N.
    Chanock, S.
    Dean, M.
    Yeager, M.
    Schoen, R. E.
    Hou, L. F.
    Berndt, S. I.
    Yadavalli, S.
    Johnson, C. C.
    Hayes, R. B.

  2. Author Address

    NCI, Div Canc Epidemiol & Genet, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD USA. Univ Pittsburgh, Div Gastroenterol, Pittsburgh, PA 15260 USA. Henry Ford Hlth Sci Ctr, Josephine Ford Canc Ctr, Detroit, MI USA Huang, WY, NCI, Div Canc Epidemiol & Genet, Ctr Canc Res, NIH,Dept Hlth & Human Serv, EPS 8113,MSC 7240, Bethesda, MD 20892 USA
    1. Year: 2005
    2. Date: JAN
  2. Journal: Cancer Epidemiology Biomarkers & Prevention
    1. 14
    2. 1
    3. Pages: 152-157
  4. Type of Article: Article
  1. Abstract:

    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(113)His (exon 3) and His(139)Arg (exon 4) are associated, respectively, with low ((113)His) and high ((139)Arg) 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 2:1 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 screen-negative for left-sided adenoma. Compared to those with homozygous genotypes predicting low EPHX1 activity, advanced adenoma risks tended to be elevated for carriers of (113)TyrTyr [odds ratios (OR), 1.5; 95% confidence intervals (CI), 1.0-2.2] and (139)ArgArg (OR, 1.4; 95% CI, 0.8-2.5) and for subjects who carried a greater number of the alleles ((113)Tyr or (139)Arg) 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

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  1. View record in Web of Science®
  2. WOS: 000226534000020

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