P53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers.

In this paper we describe a statistical analysis of the European Molecular Library p53 mutation database comparing p53 mutations occurring in breast, colorectal, liver, lung, and ovarian cancers. The analyses show that mutation hot spots vary by cancer and that base pair changes and predicted amino acid changes in the gene product vary by cancer and by codon. The analyses use relative frequencies and epidemiologic measures of effect (prevalence ratios) not applied previously to these data. The five cancers in the database with the largest sample sizes were breast (418), colorectal (398), liver (341), non-small cell lung (313), and ovarian cancers (251), for a total of 1,721 reports of p53 mutations. The five cancers varied considerably in the distribution of mutations over sites, with different hot spots in each cancer. At the six most frequently reported codon sites, we compared base pair and amino acid changes by type of cancer. The comparison of base pair changes indicated a predominance of particular base pair changes at a codon (for example, C-->T and G-->A changes at Codon 248) and their association with specific cancers (C-->T changes with colorectal cancer and G-->A changes with both colorectal and breast cancers at codon 248). Comparing predicted amino acid changes by codon and cancer was also intriguing, as in codons 175 and 273, where arginine to cysteine and arginine to histidine changes were frequent in breast, colorectal, and ovarian cancers. Variations in p53 mutational distributions by cancer may be explained by different exposures to carcinogens or by organ-specific clonal selection. Further research may be stimulated by this analysis.