OBJECTIVE: Recent studies have demonstrated the importance of folate metabolic pathway (FMP) in the pathogenesis of head and neck carcinoma (HNC). Whether the genetic variation within the FMP associated genes modulates HNC remains elusive. To date, prospective, epidemiological data on the relationship of FMP gene variation with the risk of HNC are sparse. METHODS: The association between 203 tag-SNPs (tSNPs) of 15 FMP associated genes (CBS, BHMT, DHFR, FOLR1, FOLR2, FOLR3, MTHFR, MTR, MTRR, MTHFD1, RFC1, SHMT1, SLC19A1, TCN2, and TYMS) and incident HNC was investigated in 23,294 Caucasian female participants of the prospective Women's Genome Health Study. All were free of known cancer at baseline. During a 15-year follow-up period, 55 participants developed a first ever HNC. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and HNC risk assuming an additive genetic model. Haplotype-block analysis was also performed. RESULTS: A total of 11 tSNPs within DHFR, MTHFR, RFC1, and TYMS were associated with HNC risk (all p-uncorrected <0.050). Further investigation using the haplotype-block analysis revealed an association of several prespecified haplotypes of RFC1 with HNC risk (all p-uncorrected <0.050). CONCLUSION: If corroborated in other large prospective studies, the present findings suggest that genetic variation within the folate metabolic pathway gene loci examined, in particular, the replication factor C-1 (RFC1) gene variation may influence HNC risk.
OBJECTIVE: Recent studies have demonstrated the importance of folate metabolic pathway (FMP) in the pathogenesis of head and neck carcinoma (HNC). Whether the genetic variation within the FMP associated genes modulates HNC remains elusive. To date, prospective, epidemiological data on the relationship of FMP gene variation with the risk of HNC are sparse. METHODS: The association between 203 tag-SNPs (tSNPs) of 15 FMP associated genes (CBS, BHMT, DHFR, FOLR1, FOLR2, FOLR3, MTHFR, MTR, MTRR, MTHFD1, RFC1, SHMT1, SLC19A1, TCN2, and TYMS) and incident HNC was investigated in 23,294 Caucasian female participants of the prospective Women's Genome Health Study. All were free of known cancer at baseline. During a 15-year follow-up period, 55 participants developed a first ever HNC. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and HNC risk assuming an additive genetic model. Haplotype-block analysis was also performed. RESULTS: A total of 11 tSNPs within DHFR, MTHFR, RFC1, and TYMS were associated with HNC risk (all p-uncorrected <0.050). Further investigation using the haplotype-block analysis revealed an association of several prespecified haplotypes of RFC1 with HNC risk (all p-uncorrected <0.050). CONCLUSION: If corroborated in other large prospective studies, the present findings suggest that genetic variation within the folate metabolic pathway gene loci examined, in particular, the replication factor C-1 (RFC1) gene variation may influence HNC risk.
Authors: A Sapkota; C C Hsu; D Zaridze; O Shangina; N Szeszenia-Dabrowska; D Mates; E Fabiánová; P Rudnai; V Janout; I Holcatova; P Brennan; P Boffetta; M Hashibe Journal: Cancer Causes Control Date: 2008-05-30 Impact factor: 2.506
Authors: I-Min Lee; Nancy R Cook; J Michael Gaziano; David Gordon; Paul M Ridker; Joann E Manson; Charles H Hennekens; Julie E Buring Journal: JAMA Date: 2005-07-06 Impact factor: 56.272
Authors: D L Harmon; D C Shields; J V Woodside; D McMaster; J W Yarnell; I S Young; K Peng; B Shane; A E Evans; A S Whitehead Journal: Genet Epidemiol Date: 1999-11 Impact factor: 2.135
Authors: Paul M Ridker; Nancy R Cook; I-Min Lee; David Gordon; J Michael Gaziano; Joann E Manson; Charles H Hennekens; Julie E Buring Journal: N Engl J Med Date: 2005-03-07 Impact factor: 91.245
Authors: Paul M Ridker; Daniel I Chasman; Robert Y L Zee; Alex Parker; Lynda Rose; Nancy R Cook; Julie E Buring Journal: Clin Chem Date: 2007-12-10 Impact factor: 8.327