Mutations of the p53 gene in oral squamous-cell carcinomas from Sudanese dippers of nitrosamine-rich toombak and non-snuff-dippers from the Sudan andScandinavia

Using PCR-SSCP/DNA sequencing methods, we analyzed 14 oral squamous-cell ca rcinomas (OSCCs) and 8 premalignant oral lesions from different Sudanese pa tients for prevalence of mutations in exons 5 to 9 of the p53 gene in relat ion to toombak-dipping status. OSCCs(14 from Sudan, 28 from Scandinavia), a nd 3 pre-malignant oral lesions from Sudanese non-dippers were used as cont rols. A statistically significant increased incidence in mutations of the p 53 gene was found in OSCCs from toombak dippers (93%; 13/14), as compared w ith those from non-dippers in Sudan (57%; 8/14) and in Scandinavia (61%; 17 /28) respectively. In OSCCs from dippers, mutations were found in exons 5 t o 9, while in those from non-dippers they were found in exons 5, 7, 8, 9, a nd no mutations were found in exon 8 in any of the OSCCs from Sudan. Certai n types of mutations, however, were similar with respect to exposure to too mbak. OSCCs from dippers showed 15 transversions, 9 transitions, 3 insertio ns and one deletion, compared with 7 transversions, 2 transitions and one d eletion found in OSCCs from Sudanese non-dippers, and 9 transversions, 17 t ransitions and 2 insertions found in those from non-dippers in Scandinavia. No mutations were found in any of the non-malignant oral lesions in relati on to dipping or non-dipping status. These findings suggest that (i) the us e of toombak plays a significant role in induction of increased p53 gene mu tations, (ii) mutations observed were similar to those induced by tobacco-s pecific N-nitrosamines (TSNAs) in experimental animal models and those alre ady reported in toombak dippers, (iii) types of mutations associated with T SNAs were similar in the exposed and the control groups, (iv) a novel mutat ion in exon 6 was found in the OSCCs from toombak dippers, (v) the p53 exon s 5 (codon 130), 6 (codons 190, 216) and 7 (codons 229, 249, 252) mutations are probable hot spots for toombak-related OSCCs. Further studies are nece ssary to validate the increased incidence and exon locations of the p53-gen e mutations as a biomarker of malignant transformation in populations in wh ich the oral use of tobacco is habitual. (C) 1999 Wiley-Liss, Inc.