title: Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study.
abstract: BACKGROUND
  Folate-associated one-carbon metabolism (FOCM) is an important pathway in colorectal neoplasia risk but data on genetic variation in this pathway are largely limited to studies of single SNPs in selected genes.
  
  
  METHODS
  We used a comprehensive tagSNP approach to study the association between genetic variation in 11 genes in the FOCM pathway and risk of incident distal colorectal adenomas in a sigmoidoscopy-based case-control study. We included 655 cases (one or more adenomas) and 695 controls (no adenomas) recruited from one of two Kaiser Permanente clinics between 1991 and 1995. We assessed a total of 159 tagSNPs selected using Haploview Tagger as well as selected non-synonymous SNPs. We used unconditional logistic regression to model the association between SNPs and risk of distal adenomas, assuming a log-additive model.
  
  
  RESULTS
  Five SNPs in the SLC19A1 (RFC1) gene: rs1051266 (G80A), rs283895, rs2236484, rs12482346, and rs2838958 were associated with adenoma risk after correction for multiple testing (all corrected p values ≤ 0.043). The non-synonymous SLC19A1 SNP G80A interacted significantly with the MTHFR C677T genotype (interaction p value = 0.018).
  
  
  CONCLUSIONS
  Our data suggest that genetic variation in SLC19A1 may modify the risk of distal colorectal adenoma.
authors.affiliation: Department of Preventive Medicine, Genetic Epidemiology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. ajoanlev@usc.edu
authors.forename: A Joan
authors.initials: AJ
authors.lastname: Levine
authors.forename: Won
authors.initials: W
authors.lastname: Lee
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.forename: David J
authors.initials: DJ
authors.lastname: Vandenberg
authors.forename: Brian D
authors.initials: BD
authors.lastname: Davis
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Edlund
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Henning
authors.forename: David
authors.initials: D
authors.lastname: Heber
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000502:physiology; D005838:Genotype; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D058978:Reduced Folate Carrier Protein / Q000235:genetics; D012307:Risk Factors; D012812:Sigmoidoscopy
chemical_list: D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)