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Relationship between p53 mutation incidence in oral cavity squamous cell carcinomas and patient tobacco use
1Divisions of Pathology and Toxicology Valhalla, NY 10595
2Nutritional Carcinogenesis, American Health Foundation Valhalla, NY 10595
3Department of Otolaryngology. The New York Eye and Ear Infirmary New York, NY 10003
4Head and Neck Service, Memorial Sloan-Kettering Cancer Center New York, NY 10021, USA
5To whom correspondence and reprint should be addressed
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 mutationsin 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 thepredominant mutations observed in OCSCCs from tobacco users. No specific pattern of mutation was obsered 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 induce a specific pattern of mutations in oral cavity tissue in vivo.
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