Effects of Dietary Folate on Tumor Expression in the Liver of Mice with Down Syndrome

Down syndrome, or trisomy 21, is the most frequent chromosomal cause of mild to moderate intellectual disability in the United States. Research suggests persons with Down syndrome have a reduced risk of cancer due to an over expression of Down Syndrome Critical Region 1 (DSCR1) gene. DSCR1 suppresses tumor growth by inhibiting angiogenesis, the creation of new blood vessels. Folic acid, on the other hand, has been shown to increase angiogenesis. This study examined whether decreased levels of folic acid in the diet would up-regulate DSCR1, which would decrease the risk for cancer in mice with Down syndrome due to an increase in tumor suppression. Since the liver is the primary site for folate metabolism, liver tissues (n = 5) were collected from control and Down syndrome (Ts65Dn) mice. Prior to collection, the mice were fed diets consisting of folic acid supplemented (7ppm) (C = 12; DS = 9), control (2 ppm) (C = 11; DS = 10) or folic acid deficient (0 ppm) (C = 5; DS = 3) diets. The livers were made into a solution through protein isolation; concentrations were tested through protein assay, then run through Western Blots to determine relative DSCR1 expression. Comparison of the means of DSCR1 expression was expressed using a Boxplot distribution, and then analyzed using t-tests and ANOVA. The results suggest there was no significant difference between DCSR1 expression in control verses mice with Down syndrome. When comparing the means of DSCR1 expression among only mice with Down syndrome using ANOVA, there was a significant difference between DSCR1 expression and level of folate in the diet. This suggests that mice with Down syndrome on the folic acid deficient diet are at decreased risk for cancer due to increased DSCR1 expression, which is consistent with the hypothesis. The study was limited by a small sample size (n = 50) and included only 8 mice on a folic acid deficient diet (C = 5; DS = 3). Further research is needed, perhaps using brain tissue, to provide a better understanding of the relationship between folate and tumor growth in persons with Down syndrome.