CYP1A1 genetic polymorphisms and in situ colorectal cancer.
CYP1A1 genetic polymorphisms and in situ colorectal cancer.
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DOI：
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发表时间：
1994-07
期刊：
影响因子：
11.2
通讯作者：
L. Sivaraman;M. Leatham;J. Yee;L. Wilkens;A. Lau;L. Marchand
中科院分区：
文献类型：
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作者：
L. Sivaraman;M. Leatham;J. Yee;L. Wilkens;A. Lau;L. Marchand
许多研究将结直肠腺瘤与吸烟和大肠癌与食用可能含有多环芳烃的食物联系起来。最近在CYP 1A 1 3 '端MspI突变的纯合子中观察到多环芳烃的代谢活化增强。我们进行了一项基于人群的病例对照研究，以调查CYP 1A 1多态性是否与结直肠癌风险相关。采用聚合酶链反应为基础的方法，我们评估了43例大肠原位腺癌患者和129例对照人群中CYP 1A 1 3 '端MspI多态性和该基因第7外显子另一突变（Ile-Val多态性）的频率。在日本人（P = 0.008）和夏威夷人/部分夏威夷人（P < 0.001）中，发现MspI突变基因型的纯合性与原位结直肠癌正相关，而该研究缺乏在高加索人中检测类似关联的能力。在日本人中，纯合子变异基因型与杂合子和野生型基因型相比的优势比为7.9（95%置信区间，1.4-44.4）。日本人的外显子7突变纯合性也存在类似的关联，因为这两种多态性处于遗传不平衡状态。因此，这项研究表明，CYP 1A 1和多环芳烃在高基因频率人群中的结直肠癌病因学中可能具有重要作用。
Numerous studies have associated colorectal adenoma with smoking and large bowel cancer with consumption of foods potentially containing polycyclic aromatic hydrocarbons. Enhanced metabolic activation of polycyclic aromatic hydrocarbons has recently been observed in homozygotes for a MspI mutation in the 3'-end of CYP1A1. We conducted a population-based case-control study to investigate whether CYP1A1 polymorphisms were related to colorectal cancer risk. Using polymerase chain reaction-based methods, we assessed the frequency of the MspI polymorphism in the 3'-end of CYP1A1 and another mutation in exon 7 of the gene (Ile-Val polymorphism) among 43 patients with in situ adenocarcinoma of the large bowel and 129 population controls. Homozygosity for the MspI mutant genotype was found to be positively associated with in situ colorectal cancer in Japanese (P = 0.008) and Hawaiians/part-Hawaiians (P < 0.001), whereas the study lacked power to detect a similar association in Caucasians. The odds ratio for the homozygous variant genotype compared to the heterozygous and wild-type genotypes was 7.9 (95% confidence interval, 1.4-44.4) in Japanese. A similar association was suggested for the exon 7 mutation homozygosity in Japanese, as the two polymorphisms are in genetic disequilibrium. Thus, this study suggests a potentially important role for CYP1A1 and polycyclic aromatic hydrocarbons in the etiology of colorectal cancer in populations with a high gene frequency.