Vitamin D lowers the number of intestinal tumours in adult intestine-specific Apc-mutant mice only during early tumour initiation in gestation and juvenility

We reported earlier that adult FabplCre;Apc15lox/+ mice with either daily UV exposure or vitamin D supplementation developed not significantly fewer intestinal tumours but less tumour bulk (reduced outgrowth) than control mice that remained vitamin D deficient. Here, we report on a prior exploratory study in which parents (FabplCre and Apc15lox/15lox) and pups were fed either the vitamin D deficient (< 5 IU/kg) or supplemented (1500 IU/kg) diet before selecting the proper genotype and continuing on in adulthood with the respective diets. Then, a lifelong vitamin D rich diet did significantly reduce the number of intestinal tumours from 10.9 to 7.5 tumours/mouse (p = 0.02) at an age of 200 days. For this reduction, the vitamin D apparently needed to be already present in the earliest stages of tumour initiation shortly after intestinal truncation of floxed Apc alleles in utero. If our experimental results apply to other vitamin D susceptible cancer types, it may explain differences between observational studies on (long term) vitamin D statuses and randomized trials on (4-5 years) vitamin D supplementation in relation to cancer risk.