AIM: To investigate p53 mutations in esophageal cancer in a high-risk population, and correlate them with smoking, alcohol consumption and betel chewing. METHODS: One hundred and sixty-five tumor samples of esophageal squamous cell carcinoma (ESCC) obtained from a university hospital in Songkhla province, Southern Thailand were investigated for p53 mutations in exons 5-8, using polymerase chain reaction-single strand conformation polymorphism analysis, followed by direct sequencing. A polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay was additionally used to confirm possible germline mutation in intron 6. A history of risk habits was obtained by interviews. The association between risk habits and mutation frequency was evaluated using the χ(2) test. RESULTS: The studied specimens were from 139 male and 26 female patients with ESCC, treated at Songklanagarind Hospital. Most of the patients were smokers (86.7%) and alcohol consumers (72.73%), and 38.3% were betel chewers. Forty-three mutations of the p53 gene were detected in 25.5% (42/165) of tumor samples. Mutations were most commonly found in exon 5 (25.6%) and exon 8 (25.6%). Mutations in the hot-spot codon 248 were found in four cases (9.3% of all mutations). G:C→C:G (30.23%), G:C→A:T (27.90%) and G:C→T:A (16.28%) were the prevalent spectra of mutations. Unexpectedly, among 10 intronic mutations, eight cases harbored a similar mutation: G→C substitution in intron 6 (nucleotide 12759, GenBank NC_000017). These were additionally confirmed by the RFLP technique. Similar mutations were also detected in their matched blood samples using RFLP and direct sequencing, which suggested germline mutations. There was no significant correlation between risk habits and p53 mutation frequency. CONCLUSION: A proportion of Thai ESCC patients harbored specific intronic p53 mutations, which might be germline mutations. Further studies are needed to explore this novel finding.
AIM: To investigate p53 mutations in esophageal cancer in a high-risk population, and correlate them with smoking, alcohol consumption and betel chewing. METHODS: One hundred and sixty-five tumor samples of esophageal squamous cell carcinoma (ESCC) obtained from a university hospital in Songkhla province, Southern Thailand were investigated for p53 mutations in exons 5-8, using polymerase chain reaction-single strand conformation polymorphism analysis, followed by direct sequencing. A polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay was additionally used to confirm possible germline mutation in intron 6. A history of risk habits was obtained by interviews. The association between risk habits and mutation frequency was evaluated using the χ(2) test. RESULTS: The studied specimens were from 139 male and 26 female patients with ESCC, treated at Songklanagarind Hospital. Most of the patients were smokers (86.7%) and alcohol consumers (72.73%), and 38.3% were betel chewers. Forty-three mutations of the p53 gene were detected in 25.5% (42/165) of tumor samples. Mutations were most commonly found in exon 5 (25.6%) and exon 8 (25.6%). Mutations in the hot-spot codon 248 were found in four cases (9.3% of all mutations). G:C→C:G (30.23%), G:C→A:T (27.90%) and G:C→T:A (16.28%) were the prevalent spectra of mutations. Unexpectedly, among 10 intronic mutations, eight cases harbored a similar mutation: G→C substitution in intron 6 (nucleotide 12759, GenBank NC_000017). These were additionally confirmed by the RFLP technique. Similar mutations were also detected in their matched blood samples using RFLP and direct sequencing, which suggested germline mutations. There was no significant correlation between risk habits and p53 mutation frequency. CONCLUSION: A proportion of Thai ESCC patients harbored specific intronic p53 mutations, which might be germline mutations. Further studies are needed to explore this novel finding.
Authors: T A Lehman; B G Haffty; C J Carbone; L R Bishop; A A Gumbs; S Krishnan; P G Shields; R Modali; B C Turner Journal: Cancer Res Date: 2000-02-15 Impact factor: 12.701
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