生物转化酶基因多态性与前列腺癌易感性的研究

Polymorphism of metabolic gene and genetic susceptibility to prostate cancer

目的探讨生物转化酶类细胞色素P450(CYP)基因CYP1A1m1、m2和谷胱甘肽转硫酶(GST)M1基因多态性与前列腺癌易感性的关系.方法采用寡核苷酸芯片对83例前列腺癌患者(前列腺癌组)和115例非前列腺癌对照者(对照组)的中国汉族人基因组DNA进行CYP1A1、GSTM1基因多态性分析.结果 GSTM1缺失型在前列腺癌组和对照组均为48例 (57.8%,41.7%),两组比较差异有统计学意义(χ2=4.99,P＝0.025), GSTM1缺失型使患前列腺癌的危险度增加1.9倍(95%CI=1.10～3.40).GSTM1缺失型随着前列腺癌的分期、分级的提高,其相对危险度明显提高.前列腺癌组CYP1A1基因的两个多态位点m1、m2基因型频率和等位基因的频率与对照组相比均无统计学意义(P>0.05).结论中国汉族人群GSTM1缺失型可能与前列腺癌的发病风险相关,与前列腺癌的分级、分期有关,对临床预测前列腺癌预后可能有一定意义.

Objective To study the possible relationship between the single nucleotide polymorphism （SNP） of cytochrome P-450 CYP1 A1 （ CYP1 A1 ） ml, m2 and GSTM1 [ null ] genotype and genetic susceptibility to prostate cancer（ PC ）, Methods Eighty-three PC patients and 115 age-matched healthy controls were enrolled in this study. All DNA samples from peripheral blood were genotyped for genetic polymorphisms of CYP1A1 and GSTM1 genes by genechip technique. Results There was a significant difference in the frequency of GSTM1 [ null] genotype in PC cases （57.8%）compared to healthy controls（41.7% ） （ X^2 = 4. 99, P = 0. 025 ）. Individuals with the GSTM1 [ null] genotype demonstrated increased risk（ OR = 1.9, 95% CI = 1.10--1.34）. The frequency of the GSTM1 [ null] genotype was also higher in patients with advanced stage or high grade disease. There were no significant differences in the frequent distribution of two locate of CYP1 A1 polymorphisms between prostate cancer patients and healthy controls（P 〉 0.05 ）. Conclusions GSTM1 [ null] genotype may be linked to prostate caner risk in Chinese population. GSTM1 [ null] genotype was also related to the stage and grade , which may be helpful in determining the risk of locally disease and advanced PC .