RELATIONSHIP BETWEEN P53 MUTATION INCIDENCE IN ORAL CAVITY SQUAMOUS-CELL CARCINOMAS AND PATIENT TOBACCO USE

It is well-established that a high incidence of p53 mutations exist in oral cavity squamous cell carcinomas (OCSCCs), To determine whether p 53 mutations are etiologically associated with OCSCC development or ar e associated with exposure to specific carcinogens, we have analyzed t he conserved regions of the p53 gene (exons 5-9) in 48 OCSCCs obtained from patients with varied tobacco and alcohol use histories by polyme rase chain reaction/single strand conformational polymorphism (PCR/SSC P) and DNA sequencing analysis, Thirty-eight percent (18/48) of the OC SCCs exhibited a mutation in exons 5-9 of the p53 gene, There was a si gnificantly higher incidence of p53 mutations in OCSCCs from tobacco u sers (predominantly cigarette smokers) compared to those who had never used tobacco, No increase in the incidence of p53 mutation was observ ed in tobacco users who drank alcohol. G to A transitions and deletion s were the predominant mutations observed in OCSCCs from tobacco users . No specific pattern of mutation was observed in OCSCCs from those su bjects who had never used tobacco, These data suggest that a history o f tobacco use was associated with a high incidence of p53 mutations in patients with OCSCC and that tobacco carcinogens induce a specific pa ttern of mutations in oral cavity tissue in vivo.