The Price of Human Evolution: Cancer-Testis Antigens, the Decline in Male Fertility and the Increase in Cancer

The increasing frequency of general and particularly male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis antigens (CTA). The phylostratigraphy analysis of the human genome allowed us to link the early evolutionary origin of cancer via the reproductive life cycles of the unicellulars and early multicellulars, potentially driving soma-germ transition, female meiosis, and the parthenogenesis of polyploid giant cancer cells (PGCCs), with the expansion of the CTA multi-families, very late during their evolution. CTA adaptation was aided by retrovirus domestication in the unstable genomes of mammals, for protecting male fertility in stress conditions, particularly that of humans, as compensation for the energy consumption of a large complex brain which also exploited retrotransposition. We found that the early and late evolutionary branches of human cancer are united by the immunity-proto-placental network, which evolved in the Cambrian and shares stress regulators with the finely-tuned sex determination system. We further propose that social stress and endocrine disruption caused by environmental pollution with organic materials, which alter sex determination in male foetuses and further spermatogenesis in adults, bias the development of PGCC-parthenogenetic cancer by default.