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Mutations of the p53 gene in oral squamous‐cell carcinomas from sudanese dippers of nitrosamine‐rich toombak and non‐snuff‐dippers from the Sudan and Scandinavia
Author(s) -
Ibrahim Salah O.,
Vasstrand Endre N.,
Johannessen Anne C.,
Idris Ali M.,
Magnusson Bengt,
Nilsen Rune,
Lillehaug Johan R.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990517)81:4<527::aid-ijc4>3.0.co;2-2
Subject(s) - exon , biology , gene , microbiology and biotechnology , genetics , mutation , cancer research
Using PCR‐SSCP/DNA sequencing methods, we analyzed 14 oral squamous‐cell carcinomas (OSCCs) and 8 pre‐malignant oral lesions from different Sudanese patients for prevalence of mutations in exons 5 to 9 of the p53 gene in relation to toombak‐dipping status. OSCCs (14 from Sudan, 28 from Scandinavia), and 3 pre‐malignant oral lesions from Sudanese non‐dippers were used as controls. A statistically significant increased incidence in mutations of the p53 gene was found in OSCCs from toombak dippers (93%; 13/14), as compared with 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 to 9, while in those from non‐dippers they were found in exons 5, 7, 8, 9, and no mutations were found in exon 8 in any of the OSCCs from Sudan. Certain types of mutations, however, were similar with respect to exposure to toombak. OSCCs from dippers showed 15 transversions, 9 transitions, 3 insertions and one deletion, compared with 7 transversions, 2 transitions and one deletion found in OSCCs from Sudanese non‐dippers, and 9 transversions, 17 transitions and 2 insertions found in those from non‐dippers in Scandinavia. No mutations were found in any of the non‐malignant oral lesions in relation to dipping or non‐dipping status. These findings suggest that ( i ) the use of toombak plays a significant role in induction of increased p53 gene mutations, ( ii ) mutations observed were similar to those induced by tobacco‐specific N ‐nitrosamines (TSNAs) in experimental animal models and those already reported in toombak dippers, ( iii ) types of mutations associated with TSNAs were similar in the exposed and the control groups, ( iv ) a novel mutation in exon 6 was found in the OSCCs from toombak dippers, ( v ) the p53 exons 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 necessary to validate the increased incidence and exon locations of the p53 ‐gene mutations as a biomarker of malignant transformation in populations in which the oral use of tobacco is habitual. Int. J. Cancer 81:527–534, 1999. © 1999 Wiley‐Liss, Inc.