Gudmundsdottir K, Tryggvadottir L, Eyfjord J E
Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik 125, Iceland.
Cancer Epidemiol Biomarkers Prev. 2001 Nov;10(11):1169-73.
The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the GSTM1 and GSTT1 genes and an A-G polymorphism in the GSTP1 gene were investigated in relation to breast cancer risk in 500 breast cancer patients and 395 controls. The effects of the GST genotypes on the frequency and pattern of p53 mutations in 388 breast carcinomas were also studied. A suggestive trend of increasing risk of breast cancer with increasing number of G alleles of the GSTP1 was observed (P for trend, 0.11). The GSTM1 and GSTT1 polymorphisms did not show an association with breast cancer. No increase in risk was observed with a combination of genotypes. A statistically significant association was observed between the GSTT1 genotype and p53 mutation status of the tumors, with patients carrying the GSTT1 null genotype more frequently having mutations in the p53 gene compared with patients with a GSTT1 gene present (24.6% versus 12.4%; P = 0.019). There was also a suggestive trend for the GG genotype of the GSTP1 gene, but it was not statistically significant (P = 0.19). No association was observed with the type or location of mutations. We conclude that the GSTP1 and GSTT1 genes could play a role in carcinogenesis in the breast, possibly through increased frequency of mutations in tumor suppressor genes such as p53.
谷胱甘肽S-转移酶（GST）基因参与多种致癌物的代谢。在500例乳腺癌患者和395例对照中，研究了GSTM1和GSTT1基因的缺失多态性以及GSTP1基因的A-G多态性与乳腺癌风险的关系。还研究了GST基因型对388例乳腺癌中p53基因突变频率和模式的影响。观察到随着GSTP1基因G等位基因数量增加，乳腺癌风险有增加的提示性趋势（趋势P值为0.11）。GSTM1和GSTT1多态性与乳腺癌无关联。基因型组合未观察到风险增加。观察到GSTT1基因型与肿瘤的p53突变状态之间存在统计学显著关联，与存在GSTT1基因的患者相比，携带GSTT1无效基因型的患者p53基因发生突变的频率更高（24.6%对12.4%；P = 0.019）。GSTP1基因的GG基因型也有提示性趋势，但无统计学显著性（P = 0.19）。未观察到与突变类型或位置有关联。我们得出结论，GSTP1和GSTT1基因可能在乳腺癌致癌过程中发挥作用，可能是通过增加肿瘤抑制基因如p53的突变频率。
