title: Perigestational dietary folic acid deficiency protects against medulloblastoma formation in a mouse model of nevoid basal cell carcinoma syndrome.
abstract: Hereditary nevoid basal cell carcinoma syndrome (NBCCS) is caused by PTCH1 gene mutations that result in diverse neoplasms including medulloblastoma (MB). Epidemiological studies report reduced pediatric brain tumor risks associated with maternal intake of prenatal vitamins containing folic acid (FA) and FA supplements specifically. We hypothesized that low maternal FA intake during the perigestational period would increase MB incidence in a transgenic NBCCS mouse model, which carries an autosomal dominant mutation in the Ptch1 gene. Female wild-type C57BL/6 mice (n = 126) were randomized to 1 of 3 diets with differing FA amounts: 0.3 mg/kg (low), 2.0 mg/kg (control), and 8.0 mg/kg (high) 1 mo prior to mating with Ptch1 (+/-) C57BL/6 males. Females were maintained on the diet until pup weaning; the pups were then aged for tumor development. Compared to the control group, offspring MB incidence was significantly lower in the low FA group (Hazard Ratio = 0.47; 95% confidence interval 0.27-0.80) at 1 yr. No significant difference in incidence was observed between the control and high FA groups. Low maternal perigestational FA levels may decrease MB incidence in mice genetically predisposed to tumor development. Our results could have implications for prenatal FA intake recommendations in the presence of cancer syndromes.
authors.affiliation: Masonic Cancer Center and Brain Tumor Program, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Raha A
authors.initials: RA
authors.lastname: Been
authors.forename: Julie A
authors.initials: JA
authors.lastname: Ross
authors.forename: Christian W
authors.initials: CW
authors.lastname: Nagel
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hooten
authors.forename: Erica K
authors.initials: EK
authors.lastname: Langer
authors.forename: Krista J
authors.initials: KJ
authors.lastname: DeCoursin
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Marek
authors.forename: Callie L
authors.initials: CL
authors.lastname: Janik
authors.forename: Michael A
authors.initials: MA
authors.lastname: Linden
authors.forename: Robyn C
authors.initials: RC
authors.lastname: Reed
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Schutten
authors.forename: David A
authors.initials: DA
authors.lastname: Largaespada
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001478:Basal Cell Nevus Syndrome / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005494:Folic Acid Deficiency / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008527:Medulloblastoma / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism
chemical_list: D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D005492:Folic Acid
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