Duarte Eliza Carla Barroso, Ribeiro Daniela Cotta, Gomez Marcus Vinícius, Ramos-Jorge Maria Letícia, Gomez Ricardo Santiago
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Anticancer Res. 2008 Mar-Apr;28(2A):1101-6.
Genetic polymorphisms of carcinogen-metabolizing enzyme genes have been associated with the risk of oral squamous cell carcinoma and oral leukoplakia. The overexpression of p53 protein is the most common genetic alteration in head and neck cancer. In the present study the combined or isolated presence of glutathione S-transferases GSTM1, GSTT1, GSTP1, and the cytochrome P450 oxidases CYP1A1 and CYP2E1 polymorphisms and oral leukoplakia development in a Brazilian sample of individuals was investigated, together with the effect of these polymorphisms on p53 overexpression in the lesions.
The GSTM1, GSTT1 and CYP1A1 genotypes of 80 smoking patients with oral leukoplakia and 80 age and gender matched control subjects were studied by polymerase chain reaction (PCR), and CYP2E1 and GSTP1 polymorphisms by PCR and digestion. Immunohistochemical reactions were performed for p53 staining in paraffin embedded histological sections of oral leukoplakia lesions.
The GSTM1 null genotype was associated with an increased risk of oral leukoplakia development, independently of the other genes (OR 2.10). The simultaneous presence of GSTM1 and GSTT1 null genotypes was associated with an increased risk of oral leukoplakia development, independently of the other genes (OR 4.36). The oral leukoplakia lesions of patients with the GSTT1 null genotype showed a 6-fold increased risk of p53 overexpression (OR 6.61).
A positive association exists between the isolated or combined null genotype of GSTM1 and GSTT1 and oral leukoplakia development and the null GSTT1 genotype shows increased risk of p53 overexpression, in oral leukoplakia.
致癌物代谢酶基因的遗传多态性与口腔鳞状细胞癌和口腔白斑的风险相关。p53蛋白的过表达是头颈癌中最常见的基因改变。在本研究中，调查了巴西人群样本中谷胱甘肽S-转移酶GSTM1、GSTT1、GSTP1以及细胞色素P450氧化酶CYP1A1和CYP2E1多态性的联合或单独存在情况与口腔白斑发生的关系，以及这些多态性对病变中p53过表达的影响。
通过聚合酶链反应（PCR）研究了80例吸烟的口腔白斑患者和80例年龄及性别匹配的对照受试者的GSTM1、GSTT1和CYP1A1基因型，通过PCR和酶切研究CYP2E1和GSTP1多态性。对口腔白斑病变石蜡包埋组织切片进行p53染色的免疫组织化学反应。
GSTM1无效基因型与口腔白斑发生风险增加相关，独立于其他基因（比值比2.10）。GSTM1和GSTT1无效基因型同时存在与口腔白斑发生风险增加相关，独立于其他基因（比值比4.36）。GSTT1无效基因型患者的口腔白斑病变p53过表达风险增加6倍（比值比6.61）。
GSTM1和GSTT1的单独或联合无效基因型与口腔白斑发生之间存在正相关，且GSTT1无效基因型在口腔白斑中显示p53过表达风险增加。
