Singh R D, Haridas N, Shah F D, Patel J B, Shukla S N, Patel P S
Biochemistry Research Division, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.
Oral Dis. 2014 Jan;20(1):84-93. doi: 10.1111/odi.12079. Epub 2013 Feb 28.
Polymorphic variability in the enzymes involved in biotransformation of tobacco-related pro-carcinogens plays an important role in modulating oral cancer susceptibility. CYP1A12A, CYP1A12C, GSTM1 and GSTT1 polymorphisms were determined in 122 oral carcinoma cases and 127 controls from Gujarat, West India using PCR-based methods. The results revealed that the polymorphic variants of CYP1A1 gene did not show association towards oral cancer risk. The GSTM1 and GSTT1 null genotypes were found to be over-represented in patients than controls, suggesting a moderate increase in risk of oral cancer. The oral cancer risk was significantly increased in the patients having either alone or concurrent deletion of GSTM1 and GSTT1. The results also suggested significant association between tobacco habits, especially chewing, variant genotypes of CYP1A1, GSTM1 and GSTT1 and oral cancer risk. Our data have provided evidence that GST polymorphism modified the susceptibility to oral cancer and individuals with variant genotypes of the three genes with tobacco habits are at significant risk of developing oral cancer.
烟草相关前致癌物生物转化过程中所涉及酶的多态性变异在调节口腔癌易感性方面发挥着重要作用。采用基于聚合酶链反应（PCR）的方法，对来自印度西部古吉拉特邦的122例口腔癌病例和127名对照者进行了CYP1A12A、CYP1A12C、谷胱甘肽S-转移酶M1（GSTM1）和谷胱甘肽S-转移酶T1（GSTT1）基因多态性的检测。结果显示，CYP1A1基因的多态性变异与口腔癌风险无相关性。研究发现，GSTM1和GSTT1基因缺失型在患者中的比例高于对照者，提示口腔癌风险有适度增加。单独或同时缺失GSTM1和GSTT1的患者，其口腔癌风险显著增加。结果还表明，吸烟习惯，尤其是咀嚼烟草，与CYP1A1、GSTM1和GSTT1的变异基因型以及口腔癌风险之间存在显著关联。我们的数据证明，GST基因多态性改变了口腔癌易感性，具有这三个基因变异基因型且有吸烟习惯的个体患口腔癌的风险显著增加。
