Cancer selection

Abstract

Cancers are often thought to be selectively neutral. This is because most of the individuals that they kill are post-reproductive. Some cancers, however, kill the young and so select for anticancer adaptations that reduce the chance of death. These adaptations could reduce the somatic mutation rate or the selective value of a mutant clone of cells, or increase the number of stages required for neoplasia. New theory predicts that cancer selection--selection to prevent or postpone deaths due to cancer--should be especially important as animals evolve new morphologies or larger, longer-lived bodies, and might account for some of the differences in the causes of cancer between mice and men.

Evolutionary biology of cancer

“…Evolution of genes and genetic systems promoting cancer Recent studies have shown how genes promoting cancer can spread via the pleiotropic effects of strong selection in other contexts [40,41]. Thus, pediatric cancers are rare, apparently as a result of their strongly negative fitness effects, but they are concentrated in two tissues, brain and bone, that have undergone striking recent evolutionary increases in size and growth trajectories along the human lineage.…”

“…Such effects might have arisen as a byproduct of rapid shifts in the rate and timing of cell proliferation systems [42,43]. Similarly, a third tissue with high pediatric cancer rates, white blood cells, is subject to the effects of strong selection from host-parasite coevolution [41].…”

“…Several recent studies have provided evidence that, in reducing cancer risks, natural selection generates macroevolutionary constraints on morphology and development [40][41][42][43]. For example, a variant number of cervical vertebrae are strongly linked to pediatric cancer in humans, and the number of cervical vertebrae is highly conserved among most mammals [66].…”

“…Such application of a comparative, phylogenetic perspective to analyze the evolution of cancer is in its infancy, but holds tremendous promise. Comparative viewpoints on cancer also lead directly to concerns that animal models, such as mice, have less applicability to humans than is currently believed, because anticancer adaptations should be more or less unique to each species [60] and artificial selection inadvertently applied to laboratory animals has fundamentally altered their physiology and life history [41,84]. cancer from computer to laboratory to clinic (Box 3), analyses of how cancer evolves should also provide novel insights into outstanding questions in evolutionary ecology [43,47,48,55,63,66].…”

The utility of KRAS mutation analysis in differentiating a lung primary mucinous carcinoma from a metastatic colorectal mucinous carcinoma

“…Another explanation is the genetic instability of tumor cells leading to continual mutational progression with the consequent considerable phenotypic and genotypic evolution. [13] In conclusion, while the tumor heterogeneity hypothesis can explain the discordant KRAS mutation in the lung mucinous adenocarcinoma compared to the previous rectal mucinous adenocarcinoma and hence support a diagnosis of metastasis, the low frequency of intratumoral heterogeneity, the convincing CK20 negativity, and overall lepidic pattern seen in the mucinous adenocarcinoma found in the lung, led us to favor a lung primary over a metastasis from the rectal mucinous adenocarcinoma. In rare circumstances of two tumors showing the same morphology, sometimes checking for gene mutations, and even specific mutation sequence can help differentiate between two different primaries versus a metastasis.…”