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

Linda E Kelemen; Kathryn L Terry; Marc T Goodman; Penelope M Webb; Elisa V Bandera; Valerie McGuire; Mary Anne Rossing; Qinggang Wang; Ed Dicks; Jonathan P Tyrer; Honglin Song; Jolanta Kupryjanczyk; Agnieszka Dansonka‐Mieszkowska; Joanna Plisiecka‐Halasa; Agnieszka Timorek; Usha Menon; Aleksandra Gentry‐Maharaj; Simon A Gayther; Susan J Ramus; Steven A Narod; Harvey A Risch; John R McLaughlin; Nadeem Siddiqui; Rosalind Glasspool; James Paul; Karen Carty; Jacek Gronwald; Jan Lubiński; Anna Jakubowska; Cezary Cybulski; Lambertus A Kiemeney; Leon F. A. G Massuger; Anne M Altena; Katja K. H Aben; Sara H Olson; Irene Orlow; Daniel W Cramer; Douglas A Levine; Maria Bisogna; Graham G Giles; Melissa C Southey; Fiona Bruinsma; Susanne K Kjær; Estrid Høgdall; Allan Jensen; Claus K Høgdall; Lene Lundvall; Svend‐Aage Engelholm; Florian Heitz; Andreas du Bois; Philipp Harter; Ira Schwaab; Ralf Butzow; Heli Nevanlinna; Liisa M Pelttari; Arto Leminen; Pamela J Thompson; Galina Lurie; Lynne R Wilkens; Diether Lambrechts; Els Van Nieuwenhuysen; Sandrina Lambrechts; Ignace Vergote; Jonathan Beesley; Peter A Fasching; Matthias W Beckmann; Alexander Hein; Arif B Ekici; Jennifer A Doherty; Anna H Wu; Celeste L Pearce; Malcolm C Pike; Daniel Stram; Jenny Chang‐Claude; Anja Rudolph; Thilo Dörk; Matthias Dürst; Peter Hillemanns; Ingo B Runnebaum; Natalia Bogdanova; Natalia Antonenkova; Kunle Odunsi; Robert P Edwards; Joseph L Kelley; Francesmary Modugno; Roberta B Ness; Beth Y Karlan; Christine Walsh; Jenny Lester; Sandra Orsulic; Brooke L Fridley; Robert A Vierkant; Julie M Cunningham; Xifeng Wu; Karen Lu; Dong Liang; Michelle A.T Hildebrandt; Rachel Palmieri Weber; Edwin S Iversen; Shelley S Tworoger; Elizabeth M Poole; Helga B Salvesen; Camilla Krakstad; Line Bjorge; Ingvild L Tangen; Tanja Pejovic; Yukie Bean; Melissa Kellar; Nicolas Wentzensen; Louise A Brinton; Jolanta Lissowska; Montserrat Garcia‐Closas; Ian G Campbell; Diana Eccles; Alice S Whittemore; Weiva Sieh; Joseph H Rothstein; Hoda Anton‐Culver; Argyrios Ziogas; Catherine M Phelan; Kirsten B Moysich; Ellen L Goode; Joellen M Schildkraut; Andrew Berchuck; Paul D.P Pharoah; Thomas A Sellers; Angela Brooks‐Wilson; Linda S Cook; AOCS Study Group/ACS Investigators; Nhu D Le

doi:10.1002/mnfr.201400068

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

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

Linda E Kelemen, Kathryn L Terry, Marc T Goodman, Penelope M Webb, Elisa V Bandera, Valerie McGuire, Mary Anne Rossing, Qinggang Wang, Ed Dicks, Jonathan P Tyrer, …

Molecular nutrition & food research, Vol.58(10), pp.2023-2035

10/2014

DOI: https://doi.org/10.1002/mnfr.201400068

PMCID: PMC4197821

PMID: 25066213

Abstract

Case‐control

Dihydropyrimidine dehydrogenase

Folate

Polymorphism

Serine hydroxymethyltransferase 1 (soluble)

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 (pinteraction = 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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Title: Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk
Creators: Linda E Kelemen - University of Calgary
Kathryn L Terry - Harvard School of Public Health
Marc T Goodman - Community and Population Health Research Institute, Cedars‐Sinai Medical Center
Penelope M Webb - QIMR Berghofer Medical Research Institute
Elisa V Bandera - The State University of New Jersey
Valerie McGuire - Stanford University School of Medicine
Mary Anne Rossing - University of Washington
Qinggang Wang - Alberta Health Services‐Cancer Care
Ed Dicks - University of Cambridge
Jonathan P Tyrer - University of Cambridge
Honglin Song - University of Cambridge
Jolanta Kupryjanczyk - The Maria Sklodowska‐Curie Memorial Cancer Center and Institute of Oncology
Agnieszka Dansonka‐Mieszkowska - The Maria Sklodowska‐Curie Memorial Cancer Center and Institute of Oncology
Joanna Plisiecka‐Halasa - The Maria Sklodowska‐Curie Memorial Cancer Center and Institute of Oncology
Agnieszka Timorek - Warsaw Medical University and Brodnowski Hospital
Usha Menon - Gynaecological Cancer Research Centre, University College London
Aleksandra Gentry‐Maharaj - Gynaecological Cancer Research Centre, University College London
Simon A Gayther - University of Southern California
Susan J Ramus - University of Southern California
Steven A Narod - University of Toronto
Harvey A Risch - Yale School of Public Health
John R McLaughlin - Prosserman Centre for Health Research at the Samuel Lunenfeld Research Institute
Nadeem Siddiqui - Glasgow Royal Infirmary
Rosalind Glasspool - The Beatson West of Scotland Cancer Centre
James Paul - The Beatson West of Scotland Cancer Centre
Karen Carty - The Beatson West of Scotland Cancer Centre
Jacek Gronwald - Pomeranian Medical University
Jan Lubiński - Pomeranian Medical University
Anna Jakubowska - Pomeranian Medical University
Cezary Cybulski - Pomeranian Medical University
Lambertus A Kiemeney - Comprehensive Cancer Center
Leon F. A. G Massuger - Radboud University Medical Center
Anne M Altena - Radboud University Medical Center
Katja K. H Aben - Comprehensive Cancer Center
Sara H Olson - Department of Epidemiology and Biostatistics
Irene Orlow - Department of Epidemiology and Biostatistics
Daniel W Cramer - Harvard School of Public Health
Douglas A Levine - Gynecology Service, Memorial Sloan‐Kettering Cancer Center
Maria Bisogna - Gynecology Service, Memorial Sloan‐Kettering Cancer Center
Graham G Giles - Monash University
Melissa C Southey - University of Melbourne
Fiona Bruinsma - Cancer Council Victoria
Susanne K Kjær - University of Copenhagen
Estrid Høgdall - University of Copenhagen
Allan Jensen - Danish Cancer Society Research Center
Claus K Høgdall - University of Copenhagen
Lene Lundvall - University of Copenhagen
Svend‐Aage Engelholm - University of Copenhagen
Florian Heitz - Dr. Horst Schmidt Kliniken Wiesbaden
Andreas du Bois - Dr. Horst Schmidt Kliniken Wiesbaden
Philipp Harter - Dr. Horst Schmidt Kliniken Wiesbaden
Ira Schwaab - Praxis für Humangenetik
Ralf Butzow - University of Helsinki and Helsinki University Central Hospital
Heli Nevanlinna - University of Helsinki and Helsinki University Central Hospital
Liisa M Pelttari - University of Helsinki and Helsinki University Central Hospital
Arto Leminen - University of Helsinki and Helsinki University Central Hospital
Pamela J Thompson - Community and Population Health Research Institute, Cedars‐Sinai Medical Center
Galina Lurie - University of Hawaii Cancer Center
Lynne R Wilkens - University of Hawaii Cancer Center
Diether Lambrechts - University of Leuven
Els Van Nieuwenhuysen - University Hospitals Leuven
Sandrina Lambrechts - University Hospitals Leuven
Ignace Vergote - University Hospitals Leuven
Jonathan Beesley - QIMR Berghofer Medical Research Institute
Peter A Fasching - University of California at Los Angeles
Matthias W Beckmann - Comprehensive Cancer Center Erlangen‐EMN
Alexander Hein - Comprehensive Cancer Center Erlangen‐EMN
Arif B Ekici - Comprehensive Cancer Center Erlangen‐EMN
Jennifer A Doherty - The Geisel School of Medicine at Dartmouth
Anna H Wu - University of Southern California
Celeste L Pearce - University of Southern California
Malcolm C Pike - Department of Epidemiology and Biostatistics
Daniel Stram - University of Southern California
Jenny Chang‐Claude - German Cancer Research Center (DKFZ)
Anja Rudolph - German Cancer Research Center (DKFZ)
Thilo Dörk - Hannover Medical School
Matthias Dürst - Jena University Hospital‐Friedrich Schiller University
Peter Hillemanns - Hannover Medical School
Ingo B Runnebaum - Jena University Hospital‐Friedrich Schiller University
Natalia Bogdanova - Hannover Medical School
Natalia Antonenkova - Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N
Kunle Odunsi - Roswell Park Cancer Institute
Robert P Edwards - University of Pittsburgh
Joseph L Kelley - University of Pittsburgh
Francesmary Modugno - University of Pittsburgh
Roberta B Ness - The University of Texas School of Public Health
Beth Y Karlan - Cedars‐Sinai Medical Center
Christine Walsh - Cedars‐Sinai Medical Center
Jenny Lester - Cedars‐Sinai Medical Center
Sandra Orsulic - Cedars‐Sinai Medical Center
Brooke L Fridley - University of Kansas Medical Center
Robert A Vierkant - Mayo Clinic
Julie M Cunningham - Mayo Clinic
Xifeng Wu - The University of Texas MD Anderson Cancer Center
Karen Lu - The University of Texas MD Anderson Cancer Center
Dong Liang - Texas Southern University
Michelle A.T Hildebrandt - The University of Texas MD Anderson Cancer Center
Rachel Palmieri Weber - Duke University Medical Center
Edwin S Iversen - Duke University
Shelley S Tworoger - Brigham and Women's Hospital and Harvard Medical School
Elizabeth M Poole - Brigham and Women's Hospital and Harvard Medical School
Helga B Salvesen - University of Bergen
Camilla Krakstad - University of Bergen
Line Bjorge - University of Bergen
Ingvild L Tangen - University of Bergen
Tanja Pejovic - Oregon Health & Science University
Yukie Bean - Oregon Health & Science University
Melissa Kellar - Oregon Health & Science University
Nicolas Wentzensen - National Cancer Institute
Louise A Brinton - National Cancer Institute
Jolanta Lissowska - M. Sklodowska‐Curie Memorial Cancer Center and Institute of Oncology
Montserrat Garcia‐Closas - UK and Breakthrough Breast Cancer Research Centre
Ian G Campbell - Peter MacCallum Cancer Centre
Diana Eccles - University of Southampton
Alice S Whittemore - Stanford University School of Medicine
Weiva Sieh - Stanford University School of Medicine
Joseph H Rothstein - Stanford University School of Medicine
Hoda Anton‐Culver - University of California Irvine
Argyrios Ziogas - University of California Irvine
Catherine M Phelan - H. Lee Moffitt Cancer Center and Research Institute
Kirsten B Moysich - Roswell Park Cancer Institute
Ellen L Goode - Mayo Clinic
Joellen M Schildkraut - Duke Cancer Institute
Andrew Berchuck - Duke University Medical Center
Paul D.P Pharoah - University of Cambridge
Thomas A Sellers - H. Lee Moffitt Cancer Center and Research Institute
Angela Brooks‐Wilson - Simon Fraser University
Linda S Cook - University of New Mexico
AOCS Study Group/ACS Investigators
Nhu D Le - BC Cancer Agency
Publication Details: Molecular nutrition & food research, Vol.58(10), pp.2023-2035
Date published: 10/2014
Number of pages: 13
Grant note: the Danish Cancer Society (94‐222‐52) US Army Medical Research and Material Command (DAMD17‐98‐1‐ 8659; DAMD17‐01‐1‐0729; DAMD17‐02‐1‐0666; DAMD17‐02‐1‐0669; W81XWH‐10‐1‐0280; W81XWH‐07‐0449) European Commission's Seventh Framework Programme grant (223175—HEALTH‐F2‐2009‐223175) the American Cancer Society (CRTG‐00‐196‐01‐CCE) Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689) Norwegian Cancer Society Cancer Council Queensland Norwegian Research Council the Polish Ministry of Science and Higher Education (4 PO5C 028 14; 2 PO5A 068 27) Mayo Foundation US Public Health Service (PSA‐042205) California Cancer Research Program (00‐01389V‐20170, N01‐CN25403, 2II0200) Radboud University Medical Center National Health and Medical Research Council (NHMRC) of Australia (199600; 209057; 251533; 396414; 400281; 504715) Sigrid Juselius Foundation National Cancer Institute (K07‐CA080668) American Cancer Society Early Detection Professorship (SIOP‐06‐258‐01‐ COUN) OHSU Foundation Pomeranian Medical University US National Cancer Institute (K07‐CA095666; K07‐CA143047; K22‐CA138563; N01‐CN55424; N01‐PC067010; N01‐PC035137; P01‐CA017054; P01‐CA087696; P30‐CA15083; P50‐CA105009; P50‐ CA136393; R01‐CA014089; R01‐CA016056; R01‐CA017054; R01‐CA049449; R01‐CA050385; R01‐CA054419; R01‐CA058598; R01‐CA058860; R01‐CA061107; R01‐CA061132; R01‐CA063682; R01‐CA064277; R01‐CA067262; R01‐CA071766; R01‐CA074850; R01‐CA076016; R01‐CA080742; R01‐CA080978; R01‐CA083918; R01‐CA087538; R01‐CA092044; R01‐095023; R01‐CA106414; R01‐CA122443; R01‐CA112523; R01‐CA114343; R01‐CA126841; R01‐ CA136924; R01‐CA149429; R03‐CA113148; R03‐CA115195; R37‐CA070867; R37‐CA70867; U01‐CA069417; U01‐CA071966) German Federal Ministry of Education and Research of Germany Imperial Experimental Cancer Research Centre (C1312/A15589) Cancer Council Victoria Cancer Council Tasmania WorkSafeBC 14 Program of Clinical Biomedical Research (01GB 9401) Helsinki University Central Hospital Research Fund Cancer Council New South Wales Canadian Institutes of Health Research Investigator award (MSH‐87734) German Cancer Research Center Fred C. and Katherine B. Andersen Foundation Canadian Institutes of Health Research (MOP‐84340) Cancer Institute of New Jersey Roswell Park Cancer Institute Alliance Foundation Rudolf‐Bartling Foundation Minnesota Ovarian Cancer Alliance OvCaRe: BC's Ovarian Cancer Research Team Celma Mastry Ovarian Cancer Foundation UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge and the University College London Hospitals Mermaid I project Helse Vest NHMRC of Australia Nationaal Kankerplan of Belgium Royal Marsden Hospital Cancer Council South Australia Cancer Foundation of Western Australia ELAN Program of the University of Erlangen‐Nuremberg Ovarian Cancer Research Fund (PPD/RPCI.07) Lon V. Smith Foundation (LVS‐39420) US National Cancer Institute GAME‐ON Post‐GWAS Initiative (U19‐CA148112) L & S Milken Foundation state of Baden‐Württemberg through Medical Faculty of the University of Ulm (P.685) Canadian Institutes of Health Research (MOP‐86727) Eve Appeal (Oak Foundation) US National Institutes of Health/National Center for Research Resources/General Clinical Research Center (MO1‐RR000056)
Academic Unit: Cancer Epidemiology and Health Outcomes
Language: English
Resource Type: Journal article
Identifiers: 991031665870204646