p53 website and analysis of p53 gene mutations in human cancer: Forging a link between epidemiology and carcinogenesis

The p53 tumor suppressor gene has proven to be one of the genes most often mutated in human cancers. It involves mainly point mutations leading to ami no acid substitutions in the central region of the protein which impairs no rmal functions. Analysis of the mutational events that target the p53 gene has revealed evidence for both exogenous and endogenous mutational mechanis ms. For example, the p53 mutational spectrum reveals evidence for a direct causal effect of ultraviolet radiation in skin cancer, of aflatoxin B1 in l iver cancer, and of tobacco smoke in lung cancer. This novel field, molecul ar epidemiology of human cancer risk, has added a new dimension to classica l associative epidemiology by providing a direct link between human cancer and carcinogen exposure. For such analysis, we devised a generic software c alled UMD (Universal Mutation Database). It was developed as a generic soft ware to create locus-specific databases (LSDBs) with the 4(th) Dimension(R) package from ACI. This software includes an optimized structure to assist and secure data entry and to allow the input of various clinical data. Hum Mutat 15:105-113, 2000. (C) 2000 Wiley-Liss, Inc.