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Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.

Publication ,  Journal Article
Kelemen, LE; Terry, KL; Goodman, MT; Webb, PM; Bandera, EV; McGuire, V; Rossing, MA; Wang, Q; Dicks, E; Tyrer, JP; Song, H; Kupryjanczyk, J ...
Published in: Mol Nutr Food Res
October 2014

SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10⁻⁵) and rs828054 (OR = 1.06; p = 1 × 10⁻⁴). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10⁻⁶) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1-C transfer, previously reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03-0.006). CONCLUSION: Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-by-folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.

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Published In

Mol Nutr Food Res

DOI

EISSN

1613-4133

Publication Date

October 2014

Volume

58

Issue

10

Start / End Page

2023 / 2035

Location

Germany

Related Subject Headings

  • White People
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Nutrition & Dietetics
  • Neoplasm Proteins
  • Multivariate Analysis
  • Humans
  • Global Health
  • Genome-Wide Association Study
 

Citation

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Kelemen, L. E., Terry, K. L., Goodman, M. T., Webb, P. M., Bandera, E. V., McGuire, V., … Le, N. D. (2014). Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk. Mol Nutr Food Res, 58(10), 2023–2035. https://doi.org/10.1002/mnfr.201400068
Kelemen, Linda E., Kathryn L. Terry, Marc T. Goodman, Penelope M. Webb, Elisa V. Bandera, Valerie McGuire, Mary Anne Rossing, et al. “Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.Mol Nutr Food Res 58, no. 10 (October 2014): 2023–35. https://doi.org/10.1002/mnfr.201400068.
Kelemen LE, Terry KL, Goodman MT, Webb PM, Bandera EV, McGuire V, et al. Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk. Mol Nutr Food Res. 2014 Oct;58(10):2023–35.
Kelemen, Linda E., et al. “Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.Mol Nutr Food Res, vol. 58, no. 10, Oct. 2014, pp. 2023–35. Pubmed, doi:10.1002/mnfr.201400068.
Kelemen LE, Terry KL, Goodman MT, Webb PM, Bandera EV, McGuire V, Rossing MA, Wang Q, Dicks E, Tyrer JP, Song H, Kupryjanczyk J, Dansonka-Mieszkowska A, Plisiecka-Halasa J, Timorek A, Menon U, Gentry-Maharaj A, Gayther SA, Ramus SJ, Narod SA, Risch HA, McLaughlin JR, Siddiqui N, Glasspool R, Paul J, Carty K, Gronwald J, Lubiński J, Jakubowska A, Cybulski C, Kiemeney LA, Massuger LFAG, van Altena AM, Aben KKH, Olson SH, Orlow I, Cramer DW, Levine DA, Bisogna M, Giles GG, Southey MC, Bruinsma F, Kjaer SK, Høgdall E, Jensen A, Høgdall CK, Lundvall L, Engelholm S-A, Heitz F, du Bois A, Harter P, Schwaab I, Butzow R, Nevanlinna H, Pelttari LM, Leminen A, Thompson PJ, Lurie G, Wilkens LR, Lambrechts D, Van Nieuwenhuysen E, Lambrechts S, Vergote I, Beesley J, AOCS Study Group/ACS Investigators, Fasching PA, Beckmann MW, Hein A, Ekici AB, Doherty JA, Wu AH, Pearce CL, Pike MC, Stram D, Chang-Claude J, Rudolph A, Dörk T, Dürst M, Hillemanns P, Runnebaum IB, Bogdanova N, Antonenkova N, Odunsi K, Edwards RP, Kelley JL, Modugno F, Ness RB, Karlan BY, Walsh C, Lester J, Orsulic S, Fridley BL, Vierkant RA, Cunningham JM, Wu X, Lu K, Liang D, Hildebrandt MAT, Weber RP, Iversen ES, Tworoger SS, Poole EM, Salvesen HB, Krakstad C, Bjorge L, Tangen IL, Pejovic T, Bean Y, Kellar M, Wentzensen N, Brinton LA, Lissowska J, Garcia-Closas M, Campbell IG, Eccles D, Whittemore AS, Sieh W, Rothstein JH, Anton-Culver H, Ziogas A, Phelan CM, Moysich KB, Goode EL, Schildkraut JM, Berchuck A, Pharoah PDP, Sellers TA, Brooks-Wilson A, Cook LS, Le ND. Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk. Mol Nutr Food Res. 2014 Oct;58(10):2023–2035.
Journal cover image

Published In

Mol Nutr Food Res

DOI

EISSN

1613-4133

Publication Date

October 2014

Volume

58

Issue

10

Start / End Page

2023 / 2035

Location

Germany

Related Subject Headings

  • White People
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Nutrition & Dietetics
  • Neoplasm Proteins
  • Multivariate Analysis
  • Humans
  • Global Health
  • Genome-Wide Association Study