Mutational spectrum in the p53 gene in bladder tumors from the endemic area of black foot disease in Taiwan

• Published in: Carcinogenesis (New York) 1994-06, Vol.15 (6), p.1085-1087
• Main Authors: Shibata, Atsuko, Ohneseit, Petra F., Tsai, Yvonne C., Spruck, Charles H., Nichols, Peter W., Chiang, Han-Sun, Lai, Ming-Kuen, Jones, Peter A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; arsenic; Arsenic Poisoning; Biological and medical sciences; black foot disease; cancer; Carcinoma, Transitional Cell - etiology; Carcinoma, Transitional Cell - genetics; Female; Foot Diseases - complications; Foot Diseases - epidemiology; Genes, p53; Humans; Male; man; Medical sciences; Middle Aged; Mutation; Nephrology. Urinary tract diseases; p53 gene; p53 protein; Peripheral Vascular Diseases - complications; Peripheral Vascular Diseases - epidemiology; Poisoning - epidemiology; risk factors; Taiwan; tumor suppressor genes; Tumors of the urinary system; urinary bladder; urinary bladder carcinoma; Urinary Bladder Neoplasms - etiology; Urinary Bladder Neoplasms - genetics; Urinary tract. Prostate gland; vascular diseases; well water
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/15.6.1085

An elevated risk of bladder cancer has been reported in the endemic region of ‘black foot disease’ on the southwest coast of Taiwan and may be related to high arsenic levels in artesian well water. Thirteen urothelial tumors from this endemic region were examined for mutations in exons 5–8 of the p53 gene to identify the effects of possible exogenous factors at the DNA level. DNA was extracted from archival tissue after microdissection of tumors and analyzed by PCR-SSCP (polymerase chain reaction-based single strand conformation polymorphism), followed by direct sequencing. Eight cases (62%) showed mutations and 9 of the 10 point mutations observed were transitions. The type and position of the mutations were not significantly different when compared with the spectra of p53 mutations previously reported for transitional cell carcinomas (TCCs). However, two of the mutations were CGC→CAC base changes at codon 175, a mutational hotspot for many tumor types but previously unreported in TCCs except in cases associated with inflammatory agents. Three of the tumors examined were found to contain double mutations, a relatively rare mutagenic event in human cancers. Our results suggest that the agents responsible for the high risk of bladder cancer in the black foot disease region may operate through an inflammation- based mechanism which increases the amount of DNA damage per mutagenic event.