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.
First Department of Oral Surgery, Hokkaido University School of Dentistry, Sapporo, Japan. ic@den.hokudai.ac.jp
I
I
Chiba
M
M
Muthumala
Y
Y
Yamazaki
A
A
Uz Zaman
T
T
Iizuka
A
A
Amemiya
T
T
Shibata
H
H
Kashiwazaki
C
C
Sugiura
H
H
Fukuda
D000328:Adult; D000368:Aged; D001114:Areca / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics*; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics*; D005091:Exons; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics*; D009154:Mutation; D010946:Plants, Medicinal; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013188:Sri Lanka
D017931:DNA Primers; D004273:DNA, Neoplasm