title: Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report.
abstract: Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR=0.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk.
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle.
authors.forename: Jeong-hwa
authors.initials: JH
authors.lastname: Choi
authors.forename: Zoe
authors.initials: Z
authors.lastname: Yates
authors.forename: Charlotte
authors.initials: C
authors.lastname: Martin
authors.forename: Lyndell
authors.initials: L
authors.lastname: Boyd
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ng
authors.forename: Virginia
authors.initials: V
authors.lastname: Skinner
authors.forename: Ron
authors.initials: R
authors.lastname: Wai
authors.forename: Martin
authors.initials: M
authors.lastname: Veysey
authors.forename: Mark
authors.initials: M
authors.lastname: Lucock
mesh_terms: D018256:Adenomatous Polyps / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000483:Alleles; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004032:Diet; D044127:Epigenesis, Genetic; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D013763:Tetrahydrofolates / Q000378:metabolism
chemical_list: D013763:Tetrahydrofolates; C030371:5,6,7,8-tetrahydrofolic acid; D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase; C005984:5-methyltetrahydrofolate