Maternal B‐vitamin intake impacts on Wnt‐related genes, apoptosis and tumorigenesis in the intestine of mouse offspring

Abstract

Observations that high maternal folate intake is associated with reduced risk of several pediatric cancers led us to propose that maternal supplementation with folate and related B vitamins may also protect against colorectal cancer in offspring. Using Apc1638N mice, we showed that supplementing mothers with vitamins B2, B6, B12 and folate suppressed intestinal tumorigenesis in offspring. Maternal depletion did not increase tumor incidence but was associated with a higher prevalence of invasive tumors. We previously showed the Wnt pathway to be sensitive to B vitamin status and therefore focused on perturbations to this pathway as a possible mechanism to explain differences in tumor incidence. Expression of Apc, SFRP1, Wif-1 and Wnt5a in the intestine of offspring decreased with decreasing maternal B vitamin intake. The SFRP1 promoter was hypermethylated amongst pups of deficient dams while genomic methylation was slightly but significantly lower in offspring of deficient compared to control dams. Apoptosis was also highest amongst the deficient group while proliferation of the small intestinal mucosa was not different between groups. These data indicate that maternal B vitamin intake can impact on the methylation and expression of cancer relevant genes as well as tumorigenesis in the intestine of offspring.