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.