细胞色素P4501A1基因多态性与喉癌遗传易感性的研究

Genetic polymorphism of cytochrome P4501A1 and susceptibility to laryngeal carcinoma

目的 探讨细胞色素P45 0 1A1(cytochromep45 0 1A1,CYP1A1)MspI多态性与喉癌易感性之间的关系。方法 以病例 对照研究 ,采用聚合酶链反应 限制性片段长度多态性分析 (polymerasechainreactionrestrictionfragmentlengthpolymorphism ,PCR RFLP)方法检测 6 2例喉鳞状细胞癌和 5 6例健康对照CYP1A1的基因型 ,并按吸烟指数 (smokingindex ,SI,吸烟支数 /d×吸烟年数 )的不同分析患喉癌风险。结果 CYP1A1MspI分为野生型A、突变杂合型B和突变纯合型C的 3种基因型。杂合型B和突变纯合型C在病例组分别占 5 8 1%和 14 5 % ,对照组分别占 39 3%和 7 1% ,两两比较 ,病例组杂合型B、纯合型C显著高于对照组 ,P <0 0 5 ,比值比率 (oddsration ,OR)分别为 2 89(95 %可信限1 31～ 6 37)和 3 97(95 %可信限 1 10～ 14 2 8)。在低吸烟量组 (SI≤ 40 0 )和高吸烟剂量组 (SI >40 0 )中 ,纯合型C的OR值分别为 4 5 (95 %可信限 0 6 4～ 31 6 1)和 9(95 %可信限 1 6 0～ 5 0 74)。结论 CYP1A1MspI多态性与吸烟协同在喉癌的发生、发展中可能起重要作用。突变纯合型个体患喉癌风险增加 ,吸烟时间越长 ,量越大 。

Objective To assess the possible relation between the MspI polymorphism of Cytochrome P4501A1(CYP1A1) gene and the susceptibility to laryngeal cancer. Methods The genotypes of CYP1A1 MspI site were detected using the methods of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 62 cases of laryngeal squamous carcinoma and 56 healthy controls. Genetic risk of CYP1A1 genotypes was analyzed by smoking index (SI, cigarettes smoked per day ×years of smoking). Results Three genotypes of CYP1A1 MspI were classified into the predominant homozygotes (A), heterozygotes (B) and the rare homozygotes (C). The frequency of heterozygote B (58.1%) and genotype C (14.5%) in the patients with laryngeal cancer were higher than that of the controls (39.3%,7.1%, P<0.05), while their odds ratios were 2.89 (95% confidence interval, CI: 1.31～6.37) and 3.97 (95%CI: 1.10～14.28),respectively. The odds ratios of genotype C was 9 (95%CI:1.60～50.74) in the high dose cigarette smoking group, but was 4.5 (95% CI: 0.64～31.61) in the low dose cigarette smoking group. Conclusions With the carcinogenesis and development of laryngeal cancer, the polymorphism of CYP1A1 gene and smoking exposure together may play an important role. The individuals with genotype C are at especially high risk of laryngeal cancer, which grows with increasing cigarette consumption.