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谷胱甘肽转移酶无效基因型、西兰花与结直肠腺瘤较低的患病率

Glutathione transferase null genotype, broccoli, and lower prevalence of colorectal adenomas.

作者信息

Lin H J, Probst-Hensch N M, Louie A D, Kau I H, Witte J S, Ingles S A, Frankl H D, Lee E R, Haile R W

机构信息

Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California 90502, USA.

出版信息

Cancer Epidemiol Biomarkers Prev. 1998 Aug;7(8):647-52.

PMID:9718215
Abstract

Cruciferous vegetables, especially broccoli, may prevent cancer through anticarcinogenic compounds. For example, broccoli contains isothiocyanates that induce carcinogen-detoxifying enzymes. Glutathione transferase enzymes conjugate isothiocyanates, leading to excretion. We hypothesized that broccoli consumption in combination with the glutathione transferase M1 (GSTM1) null genotype would be associated with a lower prevalence of colorectal adenomas because of higher isothiocyanate levels. We used a case-control study of mainly asymptomatic subjects aged 50-74 years who underwent a screening sigmoidoscopy at either of two Southern California Kaiser Permanente Medical Centers during 1991-1993. Cases (n = 459) had a first-time diagnosis of histologically confirmed adenomas detected by flexible sigmoidoscopy. Controls (n = 507) had no polyp detected. Subjects had a 45-min in-person interview for information on various risk factors and basic demographic data and completed a 126-item, semiquantitative food frequency questionnaire. Blood samples were used for GSTM1 genotyping. Subjects with the highest quartile of broccoli intake (an average of 3.7 servings per week) had an odds ratio of 0.47 (95% confidence interval, 0.30-0.73) for colorectal adenomas, compared with subjects who reportedly never ate broccoli. When stratified by GSTM1 genotype, a protective effect of broccoli was observed only among subjects with the GSTM1 null genotype (P for trend, 0.001; P for interaction, 0.01). The observed broccoli-GSTM1 interaction is compatible with an isothiocyanate mechanism.

摘要

十字花科蔬菜,尤其是西兰花,可能通过抗癌化合物预防癌症。例如,西兰花含有能诱导致癌物解毒酶的异硫氰酸盐。谷胱甘肽转移酶会使异硫氰酸盐结合,从而导致其排出体外。我们推测,由于异硫氰酸盐水平较高,食用西兰花与谷胱甘肽转移酶M1(GSTM1)基因缺失型相结合会降低结肠直肠腺瘤的患病率。我们采用病例对照研究,对象主要是50 - 74岁无症状的受试者,他们于1991 - 1993年期间在南加州凯泽永久医疗中心的两家机构之一接受了乙状结肠镜筛查。病例组(n = 459)首次诊断为经组织学确诊的乙状结肠镜检查发现的腺瘤。对照组(n = 507)未检测到息肉。受试者接受了45分钟的面对面访谈,以获取各种风险因素和基本人口统计学数据的信息,并完成了一份包含126项的半定量食物频率问卷。采集血样进行GSTM1基因分型。西兰花摄入量处于最高四分位数(平均每周3.7份)的受试者患结肠直肠腺瘤的比值比为0.47(95%置信区间,0.30 - 0.73),而据报告从未食用西兰花的受试者该比值比为1。按GSTM1基因型分层时,仅在GSTM1基因缺失型受试者中观察到西兰花的保护作用(趋势P值为0.001;交互作用P值为0.01)。观察到的西兰花 - GSTM1相互作用与异硫氰酸盐机制相符。

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