Genes involved with folate uptake and distribution and their association with colorectal cancer risk

Jane C. Figueiredo, A. Joan Levine, Won H. Lee, David V. Conti, Jenny N. Poynter, Peter T. Campbell, David Duggan, Juan Pablo Lewinger, Maria Elena Martinez, Cornelia M. Ulrich, Polly Newcomb, John Potter, Paul John Limburg, John Hopper, Mark A. Jenkins, Loic Le Marchand, John A. Baron, Robert W. Haile

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)597-608
Number of pages12
JournalCancer Causes and Control
Volume21
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Folic Acid
Colorectal Neoplasms
Genes
Microsatellite Instability
Genotype
Colonic Neoplasms
Population
Registries
Case-Control Studies
Odds Ratio
Diet
Neoplasms

Keywords

  • Case-control
  • Clinic-based
  • Colorectal cancer
  • Folate
  • Folate receptor 1 (FOLR1)
  • Folylpolyglutamate synthase (FPGS)
  • Gamma-glutamyl hydrolase (GGH) family-based
  • Polymorphisms
  • Population-based
  • Reduced folate carrier (RFC)
  • Solute carrier family 19 (SLC19A1)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Figueiredo, J. C., Levine, A. J., Lee, W. H., Conti, D. V., Poynter, J. N., Campbell, P. T., ... Haile, R. W. (2010). Genes involved with folate uptake and distribution and their association with colorectal cancer risk. Cancer Causes and Control, 21(4), 597-608. https://doi.org/10.1007/s10552-009-9489-6

Genes involved with folate uptake and distribution and their association with colorectal cancer risk. / Figueiredo, Jane C.; Levine, A. Joan; Lee, Won H.; Conti, David V.; Poynter, Jenny N.; Campbell, Peter T.; Duggan, David; Lewinger, Juan Pablo; Martinez, Maria Elena; Ulrich, Cornelia M.; Newcomb, Polly; Potter, John; Limburg, Paul John; Hopper, John; Jenkins, Mark A.; Le Marchand, Loic; Baron, John A.; Haile, Robert W.

In: Cancer Causes and Control, Vol. 21, No. 4, 04.2010, p. 597-608.

Research output: Contribution to journalArticle

Figueiredo, JC, Levine, AJ, Lee, WH, Conti, DV, Poynter, JN, Campbell, PT, Duggan, D, Lewinger, JP, Martinez, ME, Ulrich, CM, Newcomb, P, Potter, J, Limburg, PJ, Hopper, J, Jenkins, MA, Le Marchand, L, Baron, JA & Haile, RW 2010, 'Genes involved with folate uptake and distribution and their association with colorectal cancer risk', Cancer Causes and Control, vol. 21, no. 4, pp. 597-608. https://doi.org/10.1007/s10552-009-9489-6
Figueiredo, Jane C. ; Levine, A. Joan ; Lee, Won H. ; Conti, David V. ; Poynter, Jenny N. ; Campbell, Peter T. ; Duggan, David ; Lewinger, Juan Pablo ; Martinez, Maria Elena ; Ulrich, Cornelia M. ; Newcomb, Polly ; Potter, John ; Limburg, Paul John ; Hopper, John ; Jenkins, Mark A. ; Le Marchand, Loic ; Baron, John A. ; Haile, Robert W. / Genes involved with folate uptake and distribution and their association with colorectal cancer risk. In: Cancer Causes and Control. 2010 ; Vol. 21, No. 4. pp. 597-608.
@article{50d4e870c7f1449f90d83f35f2473220,
title = "Genes involved with folate uptake and distribution and their association with colorectal cancer risk",
abstract = "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.",
keywords = "Case-control, Clinic-based, Colorectal cancer, Folate, Folate receptor 1 (FOLR1), Folylpolyglutamate synthase (FPGS), Gamma-glutamyl hydrolase (GGH) family-based, Polymorphisms, Population-based, Reduced folate carrier (RFC), Solute carrier family 19 (SLC19A1)",
author = "Figueiredo, {Jane C.} and Levine, {A. Joan} and Lee, {Won H.} and Conti, {David V.} and Poynter, {Jenny N.} and Campbell, {Peter T.} and David Duggan and Lewinger, {Juan Pablo} and Martinez, {Maria Elena} and Ulrich, {Cornelia M.} and Polly Newcomb and John Potter and Limburg, {Paul John} and John Hopper and Jenkins, {Mark A.} and {Le Marchand}, Loic and Baron, {John A.} and Haile, {Robert W.}",
year = "2010",
month = "4",
doi = "10.1007/s10552-009-9489-6",
language = "English (US)",
volume = "21",
pages = "597--608",
journal = "Cancer Causes and Control",
issn = "0957-5243",
publisher = "Springer Netherlands",
number = "4",

}

TY - JOUR

T1 - Genes involved with folate uptake and distribution and their association with colorectal cancer risk

AU - Figueiredo, Jane C.

AU - Levine, A. Joan

AU - Lee, Won H.

AU - Conti, David V.

AU - Poynter, Jenny N.

AU - Campbell, Peter T.

AU - Duggan, David

AU - Lewinger, Juan Pablo

AU - Martinez, Maria Elena

AU - Ulrich, Cornelia M.

AU - Newcomb, Polly

AU - Potter, John

AU - Limburg, Paul John

AU - Hopper, John

AU - Jenkins, Mark A.

AU - Le Marchand, Loic

AU - Baron, John A.

AU - Haile, Robert W.

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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.

KW - Case-control

KW - Clinic-based

KW - Colorectal cancer

KW - Folate

KW - Folate receptor 1 (FOLR1)

KW - Folylpolyglutamate synthase (FPGS)

KW - Gamma-glutamyl hydrolase (GGH) family-based

KW - Polymorphisms

KW - Population-based

KW - Reduced folate carrier (RFC)

KW - Solute carrier family 19 (SLC19A1)

UR - http://www.scopus.com/inward/record.url?scp=77953293418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953293418&partnerID=8YFLogxK

U2 - 10.1007/s10552-009-9489-6

DO - 10.1007/s10552-009-9489-6

M3 - Article

C2 - 20037791

AN - SCOPUS:77953293418

VL - 21

SP - 597

EP - 608

JO - Cancer Causes and Control

JF - Cancer Causes and Control

SN - 0957-5243

IS - 4

ER -