Characteristics of mutations in the p53 gene in oral squamous cell carcinoma associated with betel quid chewing and cigarette smoking in Taiwanese

p53 mutations are etiologically associated with the development of oral squ amous cell carcinomas (OSCCs) or are associated with exposure to specific c arcinogens. In this study, we used PCR-single strand conformation polymorph ism and DNA sequencing to analyze the conserved regions of the p53 gene (ex ons 5-9) in OSCC tumor specimens from 187 patients with varied histories of betel quid, tobacco and alcohol use. Ninety-one of the 187 OSCCs (48.66%) showed p53 gene mutations at exons 5-9. The incidence of p53 mutations was not associated with age, sex, TNM stage, status of cigarette smoking or bet el quid chewing. However, alcohol drinkers exhibited a significantly higher incidence (57/101, 56.44%) of p53 mutations than non-users (39.53%, 34/86) (P = 0.02). The effect of alcohol on the incidence of p53 mutations was st ill statistically significant (RR = 2.24; 95% CI, 1.21-4.15) after adjustme nt for cigarette smoking and betel quid (BQ) chewing. G:C to A:T transition s were the predominant mutations observed and associated with BQ and tobacc o use. Alcohol drinking could enhance these transitions. After adjustment f or cigarette smoking and BQ chewing, alcohol drinking still showed an indep endent effect on G:C to A: T transitions (RR = 2.41; 95% CI, 1.01-5.74). Th ese findings strongly suggest an important contributive role of tobacco car cinogens to p53 mutation in this series of Taiwanese OSCCs and alcohol migh t enhance these mutagenic effects. As safrole-DNA adducts have been detecte d in 77% (23/30) of the OSCC tissues from Taiwanese oral cancer patients wi th a BQ chewing history, we cannot rule out the possibility that safrole or other carcinogens present in the BQ may cause a similar pattern of mutagen esis. Determination of the role of safrole and other carcinogens present in BQ on the pattern of p53 gene mutation in OSCC will require further study.