title: The reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C > T polymorphisms and the risk of colorectal cancer: a nested case-referent study.
abstract: OBJECTIVE
  Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case-referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C > T, to the risk of colorectal cancer, taking into account pre-diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C > T polymorphism, which were analysed in a previous study.
  
  
  METHODS
  Subjects were 220 cases and 414 matched referents from the population-based Northern Sweden Health and Disease Study.
  
  
  RESULTS
  The RFC1 80A-allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T-allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C > T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance.
  
  
  CONCLUSIONS
  These findings suggest that although the RFC1 80G > A and FOLH1 1561C > T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Eklöf
authors.forename: B
authors.initials: B
authors.lastname: Van Guelpen
authors.forename: J
authors.initials: J
authors.lastname: Hultdin
authors.forename: I
authors.initials: I
authors.lastname: Johansson
authors.forename: G
authors.initials: G
authors.lastname: Hallmans
authors.forename: R
authors.initials: R
authors.lastname: Palmqvist
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D058978:Reduced Folate Carrier Protein; D012307:Risk Factors
chemical_list: D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D006710:Homocysteine; D005492:Folic Acid