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谷胱甘肽S-转移酶P1(GSTP1)和谷胱甘肽S-转移酶A1(GSTA1)基因多态性与十字花科蔬菜摄入量在结直肠腺瘤风险中存在相互作用。

GSTP1 and GSTA1 polymorphisms interact with cruciferous vegetable intake in colorectal adenoma risk.

作者信息

Tijhuis Mariken J, Wark Petra A, Aarts Jac M M J G, Visker Marleen H P W, Nagengast Fokko M, Kok Frans J, Kampman Ellen

机构信息

Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, the Netherlands.

出版信息

Cancer Epidemiol Biomarkers Prev. 2005 Dec;14(12):2943-51. doi: 10.1158/1055-9965.EPI-05-0591.

DOI:10.1158/1055-9965.EPI-05-0591
PMID:16365014
Abstract

The possible interplay between cruciferous vegetable consumption, functional genetic variations in glutathione S-transferases (GST) M1, T1, P1, and A1, and colorectal adenomas, was investigated in a Dutch case-control study. The GSTM1 and GSTT1 deletion polymorphisms, and the single nucleotide polymorphisms in GSTP1 (A313G) and in GSTA1 (C-69T) were assessed among 746 cases who developed colorectal adenomas and 698 endoscopy-based controls without any type of colorectal polyps. High and low cruciferous vegetable consumption was defined based on a median split in the control group. High consumption was slightly positively associated with colorectal adenomas [odds ratio (OR) 1.15; 95% confidence interval, 0.92-1.44]. For GSTP1, a positive association with higher cruciferous vegetable intake was only apparent in individuals with the low-activity GSTP1 genotype (GG genotype, OR 1.94; 95% confidence interval, 1.02-3.69). This interaction was more pronounced in men, with higher age and with higher meat intake. The GSTA1 polymorphism may have a modifying role as well: the OR for higher intake compared with lower intake was 1.57 (0.93-2.65) for individuals homozygous for the low expression variant (TT genotype). This seemed to be stronger with younger age and higher red meat intake. Cruciferous vegetable consumption and the combined GSTA1 and GSTP1 genotypes showed a statistically significant interaction (P = 0.034). The GSTM1 and GSTT1 genotypes did not seem to modify the association between cruciferous vegetable intake and colorectal adenomas. In conclusion, GSTP1 and GSTA1 genotypes might modulate the association between cruciferous vegetable intake and colorectal adenomas.

摘要

在一项荷兰病例对照研究中,研究了十字花科蔬菜摄入量、谷胱甘肽S-转移酶(GST)M1、T1、P1和A1的功能基因变异与结直肠腺瘤之间可能的相互作用。在746例发生结直肠腺瘤的病例和698例无任何类型结直肠息肉的内镜检查对照中,评估了GSTM1和GSTT1缺失多态性以及GSTP1(A313G)和GSTA1(C-69T)中的单核苷酸多态性。根据对照组的中位数划分来定义十字花科蔬菜的高摄入量和低摄入量。高摄入量与结直肠腺瘤呈轻度正相关[比值比(OR)为1.15;95%置信区间为0.92-1.44]。对于GSTP1,只有在低活性GSTP1基因型(GG基因型)的个体中,才明显存在与较高十字花科蔬菜摄入量的正相关(OR为1.94;95%置信区间为1.02-3.69)。这种相互作用在男性、年龄较大者和肉类摄入量较高者中更为明显。GSTA1多态性可能也有调节作用:对于低表达变异纯合子(TT基因型)的个体,高摄入量与低摄入量相比的OR为1.57(0.93-2.65)。在年龄较小者和红肉摄入量较高者中,这种情况似乎更强。十字花科蔬菜摄入量与GSTA1和GSTP1联合基因型之间存在统计学显著的相互作用(P = 0.034)。GSTM1和GSTT1基因型似乎并未改变十字花科蔬菜摄入量与结直肠腺瘤之间的关联。总之,GSTP1和GSTA1基因型可能会调节十字花科蔬菜摄入量与结直肠腺瘤之间的关联。

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