CHARACTERISTICS OF MUTATIONS IN THE P53 GENE OF ORAL SQUAMOUS-CELL CARCINOMAS ASSOCIATED WITH BETEL-QUID CHEWING IN SRI-LANKA

Oval squamous-cell carcinoma (SCC) is the most common neoplasm in Sri Lanka, accounting for approximately 30% of all cancers in mates. Epide miologic evidence indicates that there is an unequivocal relationship between betel chewing and oral carcinogenesis, suggesting that there m ay be specific genetic targets of betel-quid ingredients. The p53 gene has been indicated to be a tumor-suppressor gene that is found in mut ated form in common human cancers; however, there are few reports abou t ''carcinogen-specific'' p53 mutation. Because of this background, pr imary resected specimens from 23 oral SCCs, 7 leukoplakias and 2 oral submucous fibrosis were collected from oral SCC patients in Sri Lanka and were used for p53 mutation analysis. Exons 5 through 8 of the P53 gene were examined by polymerase chain reaction-single-strand conforma tion polymorphism (PCR-SSCP) and direct sequencing. Mutations in the p 53 gene were frequent (10/23) in oral SCC specimens from Sri Lanka. Mo reover, the mutations clustered significantly in exon 5 (7/10) of the p53 gene, and small deletions and inclusions other than point mutation s were observed. These results indicate that I) betel-quid chewing may cause specific genetic changes, including mutation in the p53 gene; 2 ) mutations in the p53 gene are not rare events in SCC patients who ar e betel-quid chewers, which contrasts with other reports; 3) exon 5 of the p53 gene could be one of the specific targets for some betel-quid ingredients; and 4) betel-quid chewing may be a critical environmenta l factor in the development of oral SCC. (C) 1998 Wiley-Liss, Inc.