title: Genetic Variation in Glutamate Carboxypeptidase II and Interaction with Dietary Natural Vitamin C May Predict Risk for Adenomatous Polyp Occurrence.
abstract: BACKGROUND
  The C1561T variant of the glutamate carboxypeptidase II (GCPII) gene is critical for natural methylfolylpolyglutamte (methylfolate) absorption, and has been associated with perturbations in folate metabolism and disease susceptibility. However, little is known on C1561T-GCPII as a risk factor for colorectal cancer. Therefore, this study examined whether C1561T-GCPII influences folate metabolism and adenomatous polyp occurrence.
  
  
  METHODS
  164 controls and 38 adenomatous polyp cases were analysed to determine blood folate and plasma homocysteine (Hcy) level, dietary intake of natural methylfolate, synthetic pteroylglutamic acid (PteGlu), vitamin C and C1561T-GCPII genotype.
  
  
  RESULTS
  In controls and cases, 7.3 and 18.4 percent of subjects respectively, were found to have the CT genotype, increasing the risk for adenomatous polyp occurrence 2.86 times (95% CI:1.37-8.0, p=0.035). Total dietary folate, methylfolate and PteGlu intake and the level of erythrocyte folate and plasma Hcy did not predict the occurrence of an adenomatous polyp. However, dietary natural vitamin C intake was associated with adenomatous polyp risk within C1561T-GCPII CT genotype subjects (p=0.037).
  
  
  CONCLUSIONS
  The findings suggest that C1561T-GCPII variation may be associated with risk for adenomatous polyp, and vitamin C may modify risk by interacting with the variant gene, its expression product and/or folate substrates.
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, Australia E-mail : mark.lucock@newcastle.edu.au.
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: Jeongseon
authors.initials: J
authors.lastname: Kim
authors.forename: Hae Dong
authors.initials: HD
authors.lastname: Woo
authors.forename: Martin
authors.initials: M
authors.lastname: Veysey
authors.forename: Mark
authors.initials: M
authors.lastname: Lucock
mesh_terms: D018256:Adenomatous Polyps / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D004032:Diet; D005492:Folic Acid / Q000097:blood*; D005838:Genotype; D043425:Glutamate Carboxypeptidase II / Q000235:genetics* / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011624:Pteroylpolyglutamic Acids / Q000008:administration & dosage; D012307:Risk Factors; D013763:Tetrahydrofolates / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D011624:Pteroylpolyglutamic Acids; D013763:Tetrahydrofolates; D014815:Vitamins; D006710:Homocysteine; C036907:pteroylpentaglutamic acid; D005492:Folic Acid; D043425:Glutamate Carboxypeptidase II; D001205:Ascorbic Acid; C005984:5-methyltetrahydrofolate