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Characteristics of mutations in the p53 gene of oral squamous‐cell carcinomas associated with betel‐quid chewing in Sri Lanka

Oral squamous‐cell carcinoma (SCC) is the most common neoplasm in Sri Lanka, accounting for approximately 30% of all cancers in males. Epidemiologic evidence indicates that there is an unequivocal relationship between betel chewing and oral carcinogenesis, suggesting that there may be specific genetic targets of betel‐quid ingredients. The p53 gene has been indicated to be a tumor‐suppressor gene that is found in mutated form in common human cancers; however, there are few reports about “carcinogen‐specific” p53 mutation. Because of this background, primary 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 conformation polymorphism (PCR‐SSCP) and direct sequencing. Mutations in the p53 gene were frequent (10/23) in oral SCC specimens from Sri Lanka. Moreover, the mutations clustered significantly in exon 5 (7/10) of the p53 gene, and small deletions and inclusions other than point mutations were observed. These results indicate that 1) 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 are 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 environmental factor in the development of oral SCC. Int. J. Cancer 77:839–842, 1998.© 1998 Wiley‐Liss, Inc.