[Familial bladder cancer]

Abstract

Despite little evidence for a hereditary cause of most cases of bladder cancer, two different patterns of genetic involvement have been suggested: an autosomal dominant pattern that accounts for a very small number of cases and a multifactorial, polygenic pattern involving genetic and environmental interaction. Inherited homozygous defect of the glutathione S-transferase M1 gene is a good example of the latter pattern. Molecular genetic analysis has revealed two distinct molecular pathways to bladder tumorigenesis. Papillary noninvasive tumors as well as invasive disease harbor the chromosome 9 allelic loss, while carcinoma in situ contains a p53 gene mutation without an alteration of chromosome 9. The p53 gene mutations are closely associated with high grade, high stage urothelial cancers and immunohistochemical detection of the p53 protein alterations may be promising prognostic marker. Analysis of the p53 gene mutation pattern suggested a monoclonal origin for multicentric occurrence of urothelial cancers.