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

✍ Scribed by Itsuo Chiba; Malsantha Muthumala; Yutaka Yamazaki; Asad Uz Zaman; Tadashi Iizuka; Akira Amemiya; Toshiyuki Shibata; Haruhiko Kashiwazaki; Chihiro Sugiura; Hiroshi Fukuda

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: French
• Weight: 73 KB
• Volume: 77
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19980911)77:6<839::aid-ijc7>3.0.co;2-v

✦ Synopsis

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 reactionsingle-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.