The Study: By “field effect,” we don’t mean the detrimental effect on ticket sales when two Southeastern college football teams play on a field in the Bay Area. We’re talking about the phenomenon where patients are prone to extensive premalignant changes and eventual development of adjacent second malignancies after primary cancer treatment. In this study, extensive analyses of somatic mutations were performed on normal esophageal epithelial samples from subjects of a broad range of ages with normal, abnormal, or malignant esophageal epithelium in other areas. Beginning almost at birth, and in almost everyone, somatic mutations (particularly in NOTCH1) gave rise to clonal expansions throughout the esophagus. In an age-related fashion, this leads to an almost complete remodeling of the epithelium and dramatic expansion of clones with somatic driver mutations. In individuals with heavy alcohol or tobacco exposure, clonal expansion was accelerated. In the end, there was a perfect storm of positively-selected clones primed for transitioning from pro-malignant to pre-malignant to outright-malignant.
Bottom Line: The esophageal “field effect” is largely a normal ageing process that can be accelerated by the addition of mutagens. | Yokoyama, Nature 2019