Low incidence of p53 mutations in betel quid and tobacco chewing-associated oral squamous carcinoma from India

Mutations of the p53 tumor suppressor gene have been found to be the single most frequent event in human cancers. In India and other southeast Asian c ountries tobacco chewing with betel quid was attributed to be the major fac tor in oral carcinogenesis. We have analyzed 72 untreated primary oral squa mous cell carcinomas (SCCs) for mutations in the tumor suppressor gene p53 exons 4-9 by PCR-SSCP and DNA sequencing. Sequencing analysis revealed 16 m issense mutations, one silent mutation in codon 307 and four A to G substit ution polymorphism in codon 213. The incidence of p53 mutation was 21% (15 of 72) excluding the polymorphism and the silent mutation. Eight mutations were clustered in codons 266-282 of exon 8. Of the total mutation events 37 .5% were G to A transitions and 31.3% were G to T transversions. These resu lts indicate the possible involvement of tobacco derived nitrosamines and t heir adducts in the genesis of oral cancer among Indians.