Wu Szu-Hsien, Tsai Shih-Meng, Hou Ming-Feng, Lin Hung-Shiun, Hou Linda Ann, Ma Hsu, Lin Jin-Teh, Yeh Fa-Lai, Tsai Li-Yu
Division of Plastic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
Breast Cancer Res Treat. 2006 Nov;100(1):93-8. doi: 10.1007/s10549-006-9226-8. Epub 2006 Jun 7.
P450 (CYP) and glutathione S-transferase (GST) are involved in the activation and detoxification of many potential carcinogens. Although, the interaction between environmental exposure and genetic polymorphisms of cytochrome P450 2E1 (CYP2E1) and glutathione S-transferase M1 (GSTM1) in breast cancer has been assessed, the gene-gene interactions between CYP2E1 and GSTM1 related to breast cancer have not been focused on and reported. We conducted a hospital-based case-control study to investigate whether the genetic interaction effects of CYP2E1 and GSTM1 modify the risk of developing breast cancer independent of the effect of cigarette smoking and alcohol consumption. Individuals with the C2/C2 genotype of CYP2E1 had a lower risk (OR = 0.24, 95% CI = 0.08-0.74) when compared with those with the C1/C1 genotype. However, there was no significant difference (OR = 1.05, 95% CI = 0.73-1.50) in the GSTM1 genotype frequency between the cases with breast cancer and that of the controls. When individuals with the genotype of C1/C1 or C1/C2 of CYP2E1 and the wild-type of GSTM1 were compared with those of C2/C2 of CYP2E1 and the null-type of GSTM1 however, we found a significantly increased risk (OR = 3.50, 95% CI = 1.01-16.55) in the breast cancer patients. Our findings indicated a gene-gene interaction between CYP2E1 and GSTM1 was accessible to developing breast cancer in Taiwanese women without the habits of cigarette smoking and alcohol consumption even though independent effects of CYP2E1 and GSTM1 were weak or non-significant and suggest that environmental carcinogen besides cigarette and alcohol consumption could induce breast cancer.
细胞色素P450(CYP)和谷胱甘肽S-转移酶(GST)参与多种潜在致癌物的激活和解毒过程。虽然已评估环境暴露与细胞色素P450 2E1(CYP2E1)和谷胱甘肽S-转移酶M1(GSTM1)基因多态性在乳腺癌中的相互作用,但尚未关注和报道CYP2E1与GSTM1之间与乳腺癌相关的基因-基因相互作用。我们进行了一项基于医院的病例对照研究,以调查CYP2E1和GSTM1的基因相互作用效应是否会改变患乳腺癌的风险,且独立于吸烟和饮酒的影响。与C1/C1基因型个体相比,CYP2E1基因C2/C2基因型个体的风险较低(OR = 0.24,95% CI = 0.08 - 0.74)。然而,乳腺癌病例组和对照组的GSTM1基因型频率无显著差异(OR = 1.05,95% CI = 0.73 - 1.50)。然而,当比较CYP2E1基因C1/C1或C1/C2基因型与GSTM1野生型个体和CYP2E1基因C2/C2基因型与GSTM1缺失型个体时,我们发现乳腺癌患者的风险显著增加(OR = 3.50,95% CI = 1.01 - 16.55)。我们的研究结果表明,在台湾无吸烟和饮酒习惯的女性中,CYP2E1和GSTM1之间存在基因-基因相互作用,这可能与乳腺癌的发生有关,尽管CYP2E1和GSTM1的独立作用较弱或不显著,这表明除吸烟和饮酒外的环境致癌物可能诱发乳腺癌。