Here, we hypothesize that the cancer-associated single nucleotide polymorphism p.P187S (rs1800566/c.C609T) in the NADP(H):quinone oxidoreductase 1 (NQO1; EC 1.6.5.2) mediates enzyme loss-of-function through long-range site-to-site effects originating at the p.P187S site and communicated to distant functional sites through a hypothetical allosteric interaction network (Fig. 1). This evidence concerns the gene NQO1 and cancer.