Ulrich C M, Bigler J, Whitton J A, Bostick R, Fosdick L, Potter J D
Fred Hutchinson Cancer Research Center, Cancer Prevention Research Program, Seattle, Washington 98109-1024, USA.
Cancer Epidemiol Biomarkers Prev. 2001 Aug;10(8):875-82.
Microsomal epoxide hydrolase (mEH) metabolizes polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke and cooked meat. Polymorphisms in exon 3 and exon 4 of the mEH gene have been found to alter mEH activity. We investigated the association between these polymorphisms and colorectal polyps within the Minnesota Cancer Prevention Research Unit case-control study. Cases were diagnosed with colonoscopically confirmed adenomas (n = 530) or hyperplastic polyps (n = 202); controls (n = 649) were polyp-free at colonoscopy. Smoking history and meat consumption were obtained from self-administered questionnaires before colonoscopy. mEH genotypes were determined by PCR/RFLP or oligonucleotide ligation assay. The overall risks associated with exon 3 or exon 4 polymorphisms for both adenomas and hyperplastic polyps were not statistically different from 1.0. Compared with exon 3 Tyr/Tyr, 0 pack-years, risk was highest among those with the exon 3 His/His genotype and >25 pack-years of smoking [adenoma, odds ratio (OR) = 4.9 (1.9-12.8); hyperplastic, OR = 7.7 (2.5-24.0)]. Risks were not elevated among exon 4 homozygous variants, even in the presence of heavy smoking. Fried, baked, or broiled meat intake of > or =two servings/week (high) compared with < or =one serving/week was associated with a 2-fold increase in risk of adenoma. The highest risks were seen for those with the exon 3 His/His genotype and high cooked meat intake [OR = 3.3 (1.4-7.9); reference group: Tyr/Tyr, < or = 1 serving/week). Although mEH polymorphisms are not associated with an increased risk of colorectal polyps overall, genotypes that produce a slow phenotype appear to be associated with an increased risk in the presence of smoking and high intakes of cooked meat.
微粒体环氧化物水解酶（mEH）可代谢多环芳烃，后者是香烟烟雾和熟肉中存在的致癌物。已发现mEH基因外显子3和外显子4中的多态性会改变mEH活性。我们在明尼苏达癌症预防研究单位的病例对照研究中调查了这些多态性与大肠息肉之间的关联。病例经结肠镜检查确诊为腺瘤（n = 530）或增生性息肉（n = 202）；对照组（n = 649）在结肠镜检查时未发现息肉。吸烟史和肉类摄入量通过结肠镜检查前的自填问卷获得。mEH基因型通过PCR/RFLP或寡核苷酸连接分析确定。腺瘤和增生性息肉的外显子3或外显子4多态性相关的总体风险与1.0无统计学差异。与外显子3 Tyr/Tyr、0包年相比，外显子3 His/His基因型且吸烟超过25包年的人群风险最高[腺瘤，优势比（OR）= 4.9（1.9 - 12.8）；增生性息肉，OR = 7.7（2.5 - 24.0）]。外显子4纯合变异体的风险并未升高，即使存在大量吸烟情况。与每周食用≤一份相比，每周食用≥两份油炸、烘焙或烤制肉类（高摄入量）与腺瘤风险增加2倍相关。外显子3 His/His基因型且熟肉摄入量高的人群风险最高[OR = 3.3（1.4 - 7.9）；参照组：Tyr/Tyr，每周≤1份]。虽然mEH多态性总体上与大肠息肉风险增加无关，但产生慢代谢表型的基因型在存在吸烟和高熟肉摄入量的情况下似乎与风险增加有关。
