Relationship between p53 mutation incidence in oral cavity squamous cell carcinomas and patient tobacco use.
Relationship between p53 mutation incidence in oral cavity squamous cell carcinomas and patient tobacco use.
复制标题
DOI：
10.1093/carcin/17.4.733
复制
发表时间：
1996-04
期刊：
影响因子：
4.7
通讯作者：
P. Lazarus;J. Stern;N. Zwiebel;A. Fair;J. Richie;S. Schantz
中科院分区：
文献类型：
--
作者：
P. Lazarus;J. Stern;N. Zwiebel;A. Fair;J. Richie;S. Schantz
口腔鳞状细胞癌（oral cavity squamous cell carcinoma，OCSCC）中p53基因突变的发生率较高。为了确定p53突变是否与OCSCC的发生在病因上相关，或者与暴露于特定致癌物相关，我们通过聚合酶链反应/单链构象多态性（PCR/SSCP）和DNA测序分析，分析了48例OCSCC中p53基因（外显子5-9）的保守区域，这些OCSCC来自具有不同烟草和酒精使用史的患者。38%（18/48）的OCSCC在p53基因的外显子5-9处发生突变。与从未使用过烟草的人相比，烟草使用者（主要是吸烟者）的OCSCC中p53突变的发生率显著较高。饮酒的吸烟者中未观察到p53突变的发生率增加。G到A的转换和缺失是在烟草使用者的OCSCC中观察到的主要突变。在从未使用烟草的受试者的OCSCC中未观察到特定的突变模式。这些数据表明，吸烟史与口腔鳞状细胞癌患者p53突变的高发生率相关，烟草致癌物包括体内口腔组织中特定的突变模式。
It is well-established that a high incidence of p53 mutations exist in oral cavity squamous cell carcinomas (OCSCCs). To determine whether p53 mutations are etiologically associated with OCSCC development or are associated with exposure to specific carcinogens, we have analyzed the conserved regions of the p53 gene (exons 5-9) in 48 OCSCCs obtained from patients with varied tobacco and alcohol use histories by polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and DNA sequencing analysis. Thirty-eight percent (18/48) of the OCSCCs exhibited a mutation in exons 5-9 of the p53 gene. There was a significantly higher incidence of p53 mutations in OCSCCs from tobacco users (predominantly cigarette smokers) compared to those who had never used tobacco. No increase in the incidence of p53 mutation was observed in tobacco users who drank alcohol. G to A transitions and deletions were the predominant mutations observed in OCSCCs from tobacco users. No specific pattern of mutation was observed in OCSCCs from those subjects who had never used tobacco. These data suggest that a history of tobacco use was associated with a high incidence of p53 mutations in patients with OCSCC and that tobacco carcinogens include a specific pattern of mutations in oral cavity tissue in vivo.