Chenevix-Trench G, Young J, Coggan M, Board P
Queensland Institute of Medical Research, Brisbane, Australia.
Carcinogenesis. 1995 Jul;16(7):1655-7. doi: 10.1093/carcin/16.7.1655.
The M1 member of the Mu subclass of glutathione S-transferase (GSTM1) is only expressed in about 50% of individuals. In contrast, GSTT1, a member of the theta class which has been recently shown to be polymorphic, is expressed in 85% of Australian individuals. Previous studies have shown a significant excess of homozygous null GSTM1 genotypes among individuals with colorectal cancer, particularly those with proximal tumours. This suggests that GSTM1 plays a role in susceptibility to this neoplasm. In this study of 132 individuals with colorectal cancer and 200 controls, no significant excess of GSTM1 homozygous null genotypes was found among colorectal cancer patients with either a proximal or distal tumour. This suggests that the association between GSTM1 homozygous null genotypes and colorectal cancer is of smaller effect than has been reported previously using larger sample sizes. We have also examined the frequency of homozygous null GSTT1 genotypes in patients with colorectal cancer. Although the frequency was not significantly different in cases compared to control individuals, GSTT1 null homozygotes were significantly more common in patients who were diagnosed before the age of 70 years than in those who were diagnosed at an older age. This suggests that the GSTT1 genotype, and perhaps also the GSTM1 genotype for which a similar, but non-significant effect was seen, might influence the age of onset of colorectal cancer.
谷胱甘肽S-转移酶（GSTM1）μ亚类的M1成员仅在约50%的个体中表达。相比之下，θ类成员GSTT1最近被证明具有多态性，在85%的澳大利亚个体中表达。先前的研究表明，在结直肠癌患者中，尤其是近端肿瘤患者中，纯合缺失GSTM1基因型的个体明显过多。这表明GSTM1在这种肿瘤的易感性中起作用。在这项对132例结直肠癌患者和200例对照的研究中，在患有近端或远端肿瘤的结直肠癌患者中，未发现GSTM1纯合缺失基因型有明显过多的情况。这表明，与之前使用更大样本量所报道的相比，GSTM1纯合缺失基因型与结直肠癌之间的关联作用较小。我们还研究了结直肠癌患者中GSTT1纯合缺失基因型的频率。尽管病例组与对照组相比频率没有显著差异，但GSTT1纯合缺失在70岁之前被诊断的患者中比在年龄较大时被诊断的患者中明显更常见。这表明GSTT1基因型，也许还有GSTM1基因型（观察到了类似但不显著的效应）可能会影响结直肠癌的发病年龄。
