细胞色素P450 2E1基因PstⅠ多态、腌制品与大肠癌关系的病例对照研究

目的：研究代谢酶细胞色素P450 2E1基因(CYP2E1)Pst Ⅰ多态性和腌制品与大肠癌易感性的关系。方法：采用人群基础的病例对照分子流行病学研究和PCR—RFLP技术,对126例大肠癌和343名健康对照Pst Ⅰ识别的CYP2E1基因型进行检测。结果：健康对照组CYP2E1基因野生型(C1／C1)为61．8％,杂合子(C1／C2)为35．8％,突变纯合子(C2／C2)为2．4％。调整年龄性别后,结肠癌病例中突变基因型频率54．9％(52．9％ C1／C2和2．0％ C2／C2)高于对照(OR 1．979,95％ CI 1．090—3．595),但直肠癌病例与对照比较,无统计学意义。分层分析发现,突变基因型、每周1或2次和隔天或每天吃腌制品单因素作用的大肠癌OR值分别1．935、2．122和2．315,而每周1或2次 突变型、隔天或每天吃 突变型联合作用后大肠癌OR值分别为2．272和3．127。分别分析结、直肠癌,腌制品对直肠癌的危险性在食用频率为每周1或2次时,差异有统计学意义,野生型和突变型的OR值分别为2．646和2．297,两者差异无统计学意义;而结肠癌危险性只有在Pst Ⅰ突变者隔天或每天吃腌制品时才剧增,OR值4．262(1．395～13．017),为野生型的2．69倍,差异有统计学意义。结论：CYP2E1 PstⅠG→C点突变是大肠癌的遗传易感性因素,与腌制品有协同作用,该作用在结肠癌尤为明显。

Genetic polymorphism in cytochrome P450 2E1, salted food and colorectal cancer susceptibility: a case-control study

OBJECTIVE: To investigate PstI allelic variants of cytochrome P450 2E1 (CYP2E1), the interaction effect on salted food and their role in risk for colorectal cancer. METHODS: The genotypes of CYP2E1 PstI restriction fragment length polymorphism were analyzed in 126 colorectal cancer cases and 343 normal controls. The unconditional logistic regression was applied to estimate the OR and its 95% CI. RESULTS: The CYP2E1 C1/C1, C1/C2 and C2/C2 genotypes were found respectively in 61.8%, 35.8% and 2.4% of normal control, similar to rectal cancer cases. The percentage of PstI variant genotype (54.9%: 52.9% C1/C2 and 2.0% C2/C2) in colon cancer cases was significantly higher than that in controls (adjusted OR1.979, 95% CI 1.090 approximately 3.595). Stratified analysis suggested an interaction between CYP2E1 C2 allele and salted food. The odds ratio (OR) for the CYP2E1 variant genotype, salted food eaten weekly or biweekly and eaten every day or every other day were 1.935, 2.122 and 2.315, respectively, while those of salted food combined with variant genotype eaten weekly or biweekly and eaten every day or every other day were 2.272 and 3.127. The role in risk for rectal cancer was different from that for colon cancer. Whatever the CYP2E1 genotype is, the risk for rectal cancer came to marked when salted food was consumed weekly or biweekly (OR = 2.646 and 2.297, respectively). However, none but the combined effect of variant genotype and salted food eaten every day or every other day had the notably risk for colon cancer and the odds ratio suddenly increased to 4.262 (95% CI 1.395 approximately 13.017), 1.69-fold higher than that of wild genotype (P = 0.072). CONCLUSION: The CYP2E1 C2 allele is a susceptibility factor for colorectal cancer, especially for colon cancer, and there is an apparent gene-environment interaction between the susceptible genotype and salted food.