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

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, Lubinski 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, Hogdall E, Jensen A, Hogdall CK, Lundvall L, Engelholm SA, 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, Investigators ASGA, Fasching P, Beckmann M, Hein A, Ekici AB, Doherty JA, Wu AH, Pearce CL, Pike MC, Stram D, Chang-Claude J, Rudolph A, Doerk T, Duerst 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 (2014)


Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 58

Pages Range: 2023-35

Journal Issue: 10

DOI: 10.1002/mnfr.201400068

Abstract

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.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).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.

Authors with CRIS profile

Involved external institutions

University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven BE Belgium (BE) Harvard University US United States (USA) (US) Cedars-Sinai Medical Center US United States (USA) (US) University of Southern California (USC) US United States (USA) (US) Oregon Health and Science University (OSHU) US United States (USA) (US) Beatson West of Scotland Cancer Centre (BWSCC) GB United Kingdom (GB) Brigham and Women's Hospital (BWH) US United States (USA) (US) Memorial Sloan Kettering Cancer Center US United States (USA) (US) Duke University US United States (USA) (US) University of Pittsburgh US United States (USA) (US) University of Calgary CA Canada (CA) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) AU Australia (AU) The State University of New Jersey (Rutgers) US United States (USA) (US) Alberta Health Services (AHS) CA Canada (CA) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) NL Netherlands (NL) Danish Cancer Society Research Center DK Denmark (DK) University of Copenhagen DK Denmark (DK) Kliniken Essen-Mitte DE Germany (DE) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) FI Finland (FI) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu PL Poland (PL) Cancer Council Victoria AU Australia (AU) Glasgow Royal Infirmary (GRI) GB United Kingdom (GB) Mount Sinai Hospital (MSH) CA Canada (CA) University of Toronto CA Canada (CA) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie PL Poland (PL) University of Hawaii (U.H.) US United States (USA) (US) Stanford University US United States (USA) (US) Fred Hutchinson Cancer Research Center CA Canada (CA) University of Texas Health Science Center at Houston (UTHealth) US United States (USA) (US) University of Kansas Medical Center US United States (USA) (US) University of Texas MD Anderson Cancer Center US United States (USA) (US) University of South Florida (USF) US United States (USA) (US) Duke University Medical Center US United States (USA) (US) The University of Melbourne AU Australia (AU) Friedrich-Schiller-Universität Jena DE Germany (DE) Haukeland University Hospital / Haukeland universitetssykehus NO Norway (NO) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology BY Belarus (BY) National Cancer Institute (NCI) US United States (USA) (US) Roswell Park Cancer Institute US United States (USA) (US) Texas Southern University (TSU) US United States (USA) (US) British Columbia Cancer Agency CA Canada (CA) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) PL Poland (PL) University College London (UCL) GB United Kingdom (GB) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Mayo Clinic US United States (USA) (US) University of Cambridge GB United Kingdom (GB) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Yale University US United States (USA) (US) Helsingin yliopisto / University of Helsinki FI Finland (FI) University of Southampton GB United Kingdom (GB) University of California Irvine US United States (USA) (US) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) BE Belgium (BE)

How to cite

APA:

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. Molecular Nutrition & Food Research, 58(10), 2023-35. https://dx.doi.org/10.1002/mnfr.201400068

MLA:

Kelemen, Linda E., et al. "Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk." Molecular Nutrition & Food Research 58.10 (2014): 2023-35.

BibTeX: Download