Ecotones—inter-biome transition zones—the wombs of both evolution and cancer

• An ecotone is an inter-biome transition zones, where exposure to two environmental gradients induces physiological stress. • Interfaces between epithelia can be viewed as ecotones. • Cancer commonly arises in ecotones including cancer of the larynx, lungs esophagus, anus, bladder, penis, uterine cervix, and lip. • Cancer also arises in surgically created ecotones including uretero-sigmoidostomy, bladder ileal augmentation, and gastric bypass. • The physiochemical conditions at the ecotones encourage carcinogenesis. An ecotone is a concept in ecology that refers to a transition zone between two biomes such as forest–grassland. The exposure to environmental gradients induces physiological stress on bordering biotas leading to high genetic diversity, high mutation rate, and intensified selection pressures. We hypothesized that similar forces act on interfaces between epithelia, that these transitions zones can be viewed as ecotones, and that cancer develops in these sites. Examples are: carcinoma of the larynx most commonly developing in the ecotone between the squamous stratified epithelium of the upper glottis and the pseudo-stratified epithelium of the lower glottis, esophageal adenocarcinoma develops in the ecotone between the stratified squamous epithelium of the esophagus and the simple columnar stomach epithelium, anal cancer develops at the ecotone between the squamous stratified epithelium of the anoderm and the columnar epithelium of the rectum, and uterine cervix cancer that almost always develops in the ‘transformation zone’, an ecotone between the ectocervix (squamous epithelium) and endocervix (columnar epithelium). If the hypothesis is correct, surgically created ecotones should also be prone to cancer development. Indeed, the risk of cancer is increased after uretero-sigmoidostomy, ileal-bladder augmentation, and gastric bypass. The physical and chemical gradients of ecotones disrupt mucosal architecture and expose vulnerable basal cells to carcinogens. The implications of ecotones modifying surgery should be borne in mind during post-operative follow-up and when planning new surgeries. Study of the ecotone concept can elucidate and predict mechanisms in oncology and potentially also in other medical fields.