Maternal B‐vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis among offspring in the Apc+/1638N mouse

Abstract

Folate and other B‐vitamins play important roles in DNA methylation, and adequate intakes of these nutrients have been implicated in the prevention of colon cancer. Concentrations of B‐vitamins in the maternal diet may impact disease susceptibility in offspring. Therefore, we investigated the effect of maternal B‐vitamin intake on intestinal tumorigenesis in offspring. Three groups of 6‐week old female C57BL/6 mice were fed diets either deficient, replete, or supplemented with folate, vitamin B2, B6, and B12 for 4 weeks, then mated with male Apc+/1638N mice. Females remained on their respective diets throughout mating, pregnancy and the suckling period (11 weeks total). After weaning, all Apc+/1638N pups were fed a replete diet (AIN‐93), regardless of maternal diet. At 32 weeks of age, 58% and 63% of pups born to deficient and replete mothers, respectively, exhibited tumors in the small intestine compared to 21% of pups born to supplemented mothers (p<0.025). Furthermore, a higher percentage of tumors collected from pups of deficient mothers displayed invasive behavior compared to tumors from pups of replete mothers (p=0.03). These data indicate that maternal B‐vitamin supplementation suppresses tumorigenesis in Apc+/1638N offspring relative to deficient and replete maternal diets and furthermore that maternal B‐vitamin depletion accelerates the acquisition of invasive characteristics in tumors.Grant Funding Source: USDA CRIS # 1950‐5100‐074‐01S