Lee H C, Yoon Y B, Kim C Y
Department of Internal Medicine, Seoul National University College of Medicine, Korea.
Korean J Intern Med. 1997 Jun;12(2):128-36. doi: 10.3904/kjim.1997.12.2.128.
Metabolic activation is a prerequisite for the carcinogenic effect of many carcinogens, and considerable interindividual variation exists in the metabolic capacity to activate the carcinogens. The cytochromes P-450 (CYPs) are responsible for the activation mechanism, and polymorphisms of the CYPs (CYP1A1, CYP2D6, and possibly CYP2E1) are known to be related to increased susceptibility to smoking related Kreyberg type I lung cancer. The aim of this study is to clarify the relationship of genetic polymorphisms of the CYPs to susceptibility to pancreatic cancer, another smoking-related cancer.
We analyzed 45 samples from patients with pancreatic cancer and 53 samples from controls. DNA was isolated from blood samples and the CYP1A1, 2D6 and 2E1 genes were amplified by PCR. Analyzing the genotypes of the CYPs by allele-specific PCR or RFLP analysis, we assessed the allele frequencies for each mutation of the CYPs among the patients with pancreatic cancer and the controls.
The allele frequencies for the mutation in the 3'-flanking region of the CYP1A1 among the cases and the controls were 0.31 and 0.36, respectively. The allele frequencies for the exon 7 mutation of the CYP1A1 were 0.16 and 0.23, respectively, but with no statistical significance. The frequencies for the mutant c2 allele of the CYP2E1 were 0.19 and 0.30, respectively, but with no statistical significance. Two persons homozygous for a gene deletion of the CYP2D6 were observed among control subjects; other mutations were not observed among either the patients or controls.
We could not find any evidence that polymorphisms of the CYPs are associated with increased susceptibility to pancreatic cancer.
代谢活化是许多致癌物致癌作用的前提条件，并且在激活致癌物的代谢能力方面存在相当大的个体差异。细胞色素P - 450（CYPs）负责激活机制，已知CYPs（CYP1A1、CYP2D6，可能还有CYP2E1）的多态性与吸烟相关的克雷伯格I型肺癌易感性增加有关。本研究的目的是阐明CYPs基因多态性与另一种吸烟相关癌症——胰腺癌易感性之间的关系。
我们分析了45例胰腺癌患者的样本和53例对照样本。从血样中提取DNA，通过聚合酶链反应（PCR）扩增CYP1A1、2D6和2E1基因。通过等位基因特异性PCR或限制性片段长度多态性（RFLP）分析来分析CYPs的基因型，我们评估了胰腺癌患者和对照中CYPs各突变的等位基因频率。
CYP1A1 3'侧翼区域突变的病例和对照的等位基因频率分别为0.31和0.36。CYP1A1第7外显子突变的等位基因频率分别为0.16和0.23，但无统计学意义。CYP2E1突变c2等位基因的频率分别为0.19和0.30，但无统计学意义。在对照受试者中观察到2人CYP2D6基因缺失纯合；在患者或对照中均未观察到其他突变。
我们没有发现任何证据表明CYPs的多态性与胰腺癌易感性增加有关。
