Genes involved with folate uptake and distribution and their  association with colorectal cancer risk.
Folate status is an important predictor of colorectal cancer risk. Common genetic variants in genes involved in regulating cellular folate levels might also predict risk, but there are limited data on this issue. We conducted a family-based case-control association study of variants in four genes involved in folate uptake and distribution: FOLR1, FPGS, GGH and SLC19A1, using 1,750 population-based and 245 clinic-based cases of pathologically confirmed colorectal cancer and their unaffected relatives participating in the Colon Cancer Family Registries. Standardized questionnaires, administered to all participants, collected information on risk factors and diet. Standard molecular techniques were used to determine microsatellite instability (MSI) status on cases. tagSNPs (n = 29) were selected based on coverage as assessed by pairwise r2. We found no evidence that tagSNPs in these genes were associated with risk of colorectal cancer. For the SLC19A1-rs1051266 (G80A, Arg27His) missense polymorphism, the A/A genotype was not associated with risk of colorectal cancer using population-based (OR = 1.00; 95% CI = 0.81-1.23) or clinic-based (OR = 0.75; 95% CI = 0.44-1.29) families compared to the G/A and G/G genotypes. We found no evidence that the association between any tagSNP and CRC risk was modified by multivitamin use, folic acid use and dietary folate intake and total folate intake. The odds ratios were similar, irrespective of MSI status, tumor subsite and family history of colorectal cancer. In conclusion, we found no significant evidence that genetic variants in FOLR1, GGH, FPGS and SLC19A1 are associated with the risk of colorectal cancer.
Figueiredo
Jane C
JC
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1450 Biggy Street Room 1509J, Los Angeles, CA 90033, USA. janefigu@usc.edu
Levine
A Joan
AJ
Lee
Won H
WH
Conti
David V
DV
Poynter
Jenny N
JN
Campbell
Peter T
PT
Duggan
David
D
Lewinger
Juan Pablo
JP
Martinez
Maria Elena
ME
Ulrich
Cornelia M
CM
Newcomb
Polly
P
Potter
John
J
Limburg
Paul J
PJ
Hopper
John
J
Jenkins
Mark A
MA
Le Marchand
Loic
L
Baron
John A
JA
Haile
Robert W
RW
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005192:Family Health; D005260:Female; D058975:Folate Receptor 1; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D010453:Peptide Synthases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D058978:Reduced Folate Carrier Protein; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D011795:Surveys and Questionnaires; D011623:gamma-Glutamyl Hydrolase / Q000235:genetics
D002352:Carrier Proteins; C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D058973:Folate Receptors, GPI-Anchored; D026901:Membrane Transport Proteins; D011956:Receptors, Cell Surface; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D005492:Folic Acid; D011623:gamma-Glutamyl Hydrolase; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase