The gut microbiome and butyrate production are regulated by many factors including diet, genetic and epigenetic as well as developmentally, which all act to modulate the interface of pineal melatonin and CAR/HPA axis driven GR activation within the circadian rhythm and the collective influence on metabolic interactions across microenvironments in cancer pathogenesis, as well as the established tumor microenvironment. This evidence concerns the gene NR3C1 and cancer.