title: Interactions Between Genome-Wide Significant Genetic Variants and Circulating Concentrations of 25-Hydroxyvitamin D in Relation to Prostate Cancer Risk in the National Cancer Institute BPC3.
abstract: Genome-wide association studies (GWAS) have identified over 100 single nucleotide polymorphisms (SNPs) associated with prostate cancer. However, information on the mechanistic basis for some associations is limited. Recent research has been directed towards the potential association of vitamin D concentrations and prostate cancer, but little is known about whether the aforementioned genetic associations are modified by vitamin D. We investigated the associations of 46 GWAS-identified SNPs, circulating concentrations of 25-hydroxyvitamin D (25(OH)D), and prostate cancer (3,811 cases, 511 of whom died from the disease, compared with 2,980 controls-from 5 cohort studies that recruited participants over several periods beginning in the 1980s). We used logistic regression models with data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) to evaluate interactions on the multiplicative and additive scales. After allowing for multiple testing, none of the SNPs examined was significantly associated with 25(OH)D concentration, and the SNP-prostate cancer associations did not differ by these concentrations. A statistically significant interaction was observed for each of 2 SNPs in the 8q24 region (rs620861 and rs16902094), 25(OH)D concentration, and fatal prostate cancer on both multiplicative and additive scales (P ≤ 0.001). We did not find strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of 25(OH)D. The intriguing interactions between rs620861 and rs16902094, 25(OH)D concentration, and fatal prostate cancer warrant replication.
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Avenue, University Campus, Ioannina, Greece
authors.forename: Vasiliki I
authors.initials: VI
authors.lastname: Dimitrakopoulou
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Shui
authors.affiliation: Department of Epidemiology,University of Michigan School of Public Health,Ann Arbor, MI,USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Mondul
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.affiliation: National Institute for Health and Welfare (THL), Helsinki, Finland.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.affiliation: Catalan Institute of Oncology (ICO), Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Agudo
authors.affiliation: Department of Epidemiology,German Institute of Human Nutrition Potsdam-Rehbruecke,14558 Nuthetal,Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.|Department of Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.|Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: International Agency for Research on Cancer (IARC-WHO), Lyon, France.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, 750 07, Uppsala, SE, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, UK.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Department of Public Health, Section for Epidemiology, Aarhus University, Bartholins Allé 2, 8000, Aarhus C, Denmark.|Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Cancer Risk Factors and Life-Style Epidemiology Unit,Cancer Research and Prevention Institute (ISPO),50141 Florence,Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Hellenic Health Foundation,GR-115 27, Athens,Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA.|Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Medicine, Harvard Medical School, Boston, MA
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.affiliation: Department of Rheumatology, Royal North Shore Hospital, Sydney, New South Wales, Australia.|Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Department of Epidemiology, University of Washington
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA.|Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Medicine, Harvard Medical School, Boston, MA
authors.forename: Walter
authors.initials: W
authors.lastname: Willett
authors.affiliation: Aging, Brigham and Women's Hospital, Boston, MA.|VA Boston Healthcare System, Boston, MA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Meir
authors.initials: M
authors.lastname: Stampfer
authors.affiliation: Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Berg
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.affiliation: University of Washington and Harvard T.H. Chan School of Public Health, WA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.|Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
authors.forename: Konstantinos K
authors.initials: KK
authors.lastname: Tsilidis
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control; D065840:Protective Factors; D018570:Risk Assessment; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: 25-hydroxyvitamin D; BPC3; gene-environment interactions; genome-wide association studies; prostate cancer