Genetic Pre-aetiologies and How the Patterns of Mutation Incidence in Cancer Risk Genes Might Suggest a Non-genetic Origin for “Genetic Cancers”

Abstract

Cancer is a relatively common disease. This study investigated the hypothesis that mutation rates are higher in genes that can influence the onset of cancer when mutated than in genes that do not, rather than the prevailing assumption that risk genes mutate at relatively comparable rates as other genes. It is understood that cancer cells have more mutations, partly because they divide more often and confer cellular fitness, which introduces more opportunities for replication errors. However, what remained unknown was that there is a difference between oncogenes (or cancer “risk genes”) and non-risk genes. The assumption is that people generally have an age-related rate of mutation across the genome. It may differ according to a number of variables but not according to these gene groups. In this study, mutations in white United States populations, generated from pre-harvested health records data, were examined according to grouping: cancer-related genes or control genes. Four different cancer types were studied, forming a total of 600 patients. The cancers were from breast, uterine, prostate and ovarian sites. A total of 28 genes chosen at random were explored. The results revealed that risk genes averaged more mutations per nucleotide than control genes, that is: more genes bore at least one mutation, and more mutations were borne per gene, when it came to risk genes. Risk genes were between 2.07 and 2.41 times more likely to mutate than the control genes. Uterine cancer was associated with more volatile genomes than other cancers in this study, but the trends were consistent in uterine cancer as well. The results suggest that there is at least one pre-aetiology: one that favors mutations in risk genes to account for the apparent “carcino-specificity.” Where it once was thought of as “mutation(s)” lead to “cancer,” for cancers deemed to be a result of replication errors, it is more likely “pre-aetiology” leads to “mutation(s)” which lead to “cancer,” as a minimum of steps that lead to these genetic cancers. Perhaps the “pre-aetiology,” whether exogenous or intrinsic, of physical mechanism or abstract reality, once identified, could be medically or metaphysically manipulated to mimic the fewer mutations of the non-cancer-risk genes as a solution to high cancer rates in the population.