One Landscape, Many Inputs: Cancer Prevention as Cofactor-and-Gene Route-Competition

Abstract

A Hypothesis & Theory / Ideas & Speculation synthesis of one-carbon (folate) metabolism, gene–diet interaction, and cancer chemoprevention. It builds on established multistage-carcinogenesis and chemoprevention findings (including the documented harm signals of some supplement trials) and offers a candidate account of why folate form and timing, and baseline nutritional status, condition cancer-prevention outcomes in a gene-dependent way. It is a perspective; its predictions are invitations to test against that prior literature. v2 (August 2026). This version is restructured around the two discriminating predictions — an active-form window and a directional gene-by-cofactor interaction — and makes the under-identification argument falsifiable rather than assumed. Where a system's harm is already fully explained by its own chemistry, the account concedes it adds nothing there rather than subsuming the established mechanism; cross-system inclusion criteria and the multiple-comparisons hazard are stated explicitly, and several factual claims (on alcohol, vitamin D, and gene variation) are tightened. Editorial pass. Earlier versions remain in the version history.