Gertig D M, Stampfer M, Haiman C, Hennekens C H, Kelsey K, Hunter D J
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Epidemiol Biomarkers Prev. 1998 Nov;7(11):1001-5.
Glutathione S-transferase (GST) M1 and T1 genes encode GST enzymes, and are polymorphic in humans. These enzymes catalyze conjugation with glutathione, which is an important step in the detoxification of certain carcinogens. Several case-control studies have found associations of the homozygous null deletions in GSTM1 and GSTT1 with increasing the risk of colorectal and lung cancer. We prospectively examined the associations of the GSTM1 and GSTT1 polymorphisms with colorectal cancer risk in a nested case-control study (212 cases of colorectal cancer and 221 controls) within the Physicians' Health Study. Among controls, the prevalence of the GSTM1 homozygous null genotype was 53% and for GSTT1 homozygous null genotype, 23%. We found no increase in the risk of colorectal cancer for either GSTM1 null [odds ratio (OR) = 1.0; 95% confidence interval (CI), 0.7-1.5] or GSTT1 null (OR = 0.8; 95% CI, 0.5-1.2) genotypes. No differences were seen by site of colon cancer (proximal versus distal) or by age (< or = 60 years versus > 60 years). Current cigarette smokers with GSTM1 null genotype were not at an increased risk of colon cancer (OR = 1.2; 95% CI, 0.3-4.2) compared with current smokers without the null genotype; for the GSTT1 null genotype this OR was 1.1 = 95% CI (0.3-4.7). This lack of association persisted when we examined pack-years of smoking and age at starting smoking. Our results do not support an association of GSTM1 or GSTT1 polymorphisms with colorectal cancer or an interaction with cigarette smoking.
谷胱甘肽S-转移酶（GST）M1和T1基因编码GST酶，在人类中具有多态性。这些酶催化与谷胱甘肽的结合，这是某些致癌物解毒过程中的重要一步。多项病例对照研究发现，GSTM1和GSTT1基因的纯合缺失与结直肠癌和肺癌风险增加有关。我们在医师健康研究的一项巢式病例对照研究（212例结直肠癌病例和221例对照）中，前瞻性地研究了GSTM1和GSTT1基因多态性与结直肠癌风险的关系。在对照中，GSTM1纯合缺失基因型的患病率为53%，GSTT1纯合缺失基因型的患病率为23%。我们发现，GSTM1缺失（优势比[OR]=1.0；95%置信区间[CI]，0.7-1.5）或GSTT1缺失（OR=0.8；95%CI，0.5-1.2）基因型均未增加结直肠癌风险。结肠癌部位（近端与远端）或年龄（≤60岁与>60岁）之间未见差异。与无缺失基因型的现吸烟者相比，GSTM1缺失基因型的现吸烟者患结肠癌的风险并未增加（OR=1.2；95%CI，0.3-4.2）；对于GSTT1缺失基因型，该OR为1.1=95%CI（0.3-4.7）。当我们检查吸烟包年数和开始吸烟时的年龄时，这种缺乏关联的情况仍然存在。我们的结果不支持GSTM1或GSTT1基因多态性与结直肠癌有关联，也不支持与吸烟存在相互作用。
