Sivaraman L, Leatham M P, Yee J, Wilkens L R, Lau A F, Le Marchand L
Molecular Carcinogenesis Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.
Cancer Res. 1994 Jul 15;54(14):3692-5.
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.
大量研究已将结肠直肠腺瘤与吸烟以及将大肠癌与食用可能含有多环芳烃的食物联系起来。最近在CYP1A1 3'-末端MspI突变的纯合子中观察到多环芳烃的代谢活化增强。我们开展了一项基于人群的病例对照研究，以调查CYP1A1基因多态性是否与结直肠癌风险相关。我们使用基于聚合酶链反应的方法，评估了43例大肠原位腺癌患者和129名人群对照中CYP1A1 3'-末端MspI多态性以及该基因外显子7中的另一种突变（异亮氨酸-缬氨酸多态性）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大肠原位癌呈正相关，而该研究没有足够的效力检测出高加索人中的类似关联。在日本人中，与杂合子和野生型基因型相比，纯合变异基因型的优势比为7.9（95%置信区间，1.4 - 44.4）。由于这两种多态性处于遗传不平衡状态，因此在日本人中，外显子7突变纯合性也显示出类似关联。因此，本研究表明，在基因频率较高的人群中，CYP1A1和多环芳烃在结直肠癌病因学中可能起重要作用。
