The population genetics of multistage carcinogenesis.

摘要: Despite the many successes of cancer research, we lack framework necessary to predict ratio familial (inherited) sporadic (non-inherited) cancers. An evolutionary model multistage carcinogenesis provides this by demonstrating that number tumour suppressor loci (TSLs) preventing in a given tissue is expected depend upon tissue's vulnerability pre-reproductive somatic mutation. Since increases with size, single gene control human may be restricted retinoblastoma, tiny embryonic retina. The used estimate frequency mutant alleles causing inherited cancers, based on population genetics mutation-selection balance between new mutations arising and selection eliminates them. For each specific cancer, determined effectiveness which suppressed non-mutant genotype characteristic population. Effectiveness depends an interaction TSLs suppressing factors determining tissue-wide mutation rate, such as size cell divisions. predicts commonest cancers will have lowest proportion cases, associated most highest post-reproductive incidence but no elevated risk (a pattern seen epithelial cancers).