Evolution of the MUC1 gene in eutherian mammals as an adaptation responsible for the increasing incidence of cancer in humans.

The incidence of cancer in humans has been rising in association with extended life spans. Incidence rates of early onset cancers in humans <55 years of age have also been increasing for unclear reasons. One potential contributory factor is an antagonistic pleiotropy in which certain genes that appeared in mammals to increase fitness for reproduction contribute to cancer susceptibility later in life. A related concept is an evolutionary mismatch in which humans have adapted to certain environmental and dietary factors that change over time and thereby increase cancer incidence. The MUCIN 1 (MUC1) gene emerged in mammals and represents an example of antagonistic pleiotropy and evolutionary mismatch that is posited here as a contributing factor to the increasing incidence of cancer in humans. This Review focuses on the roles of MUC1 and the oncogenic M1C protein in reproductive fitness and barrier tissue protection that in settings of chronic inflammation promote pan-cancer progression and treatment resistance. Also highlighted are therapeutic approaches targeting MUC1 and M1C that are under clinical and pre-clinical development.