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Am J Epidemiol. 2017 Mar 15;185(6):452-464. doi: 10.1093/aje/kww143.

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.

Author information

1
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stavros Niarchos Avenue, University Campus, Ioannina, Greece
2
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
3
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
4
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
5
Department of Epidemiology,University of Michigan School of Public Health,Ann Arbor, MI,USA.
6
Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
7
National Institute for Health and Welfare (THL), Helsinki, Finland.
8
Catalan Institute of Oncology (ICO), Barcelona, Spain.
9
Department of Epidemiology,German Institute of Human Nutrition Potsdam-Rehbruecke,14558 Nuthetal,Germany.
10
School of Public Health, Imperial College London, London, United Kingdom.
11
Department of Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
12
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
13
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
14
Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, 750 07, Uppsala, SE, Sweden.
15
Department of Public Health and Primary Care, University of Cambridge, UK.
16
Department of Public Health, Section for Epidemiology, Aarhus University, Bartholins Allé 2, 8000, Aarhus C, Denmark.
17
Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
18
Cancer Risk Factors and Life-Style Epidemiology Unit,Cancer Research and Prevention Institute (ISPO),50141 Florence,Italy.
19
Hellenic Health Foundation,GR-115 27, Athens,Greece.
20
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA.
21
Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
22
Department of Medicine, Harvard Medical School, Boston, MA
23
Department of Rheumatology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
24
Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.
25
Department of Epidemiology, University of Washington
26
Aging, Brigham and Women's Hospital, Boston, MA.
27
VA Boston Healthcare System, Boston, MA.
28
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
29
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
30
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
31
Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, Germany.
32
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
33
Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, Illinois, USA.
34
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
35
University of Washington and Harvard T.H. Chan School of Public Health, WA, USA.
36
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
37
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

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.

KEYWORDS:

25-hydroxyvitamin D; BPC3; gene-environment interactions; genome-wide association studies; prostate cancer

PMID:
28399564
PMCID:
PMC5856084
DOI:
10.1093/aje/kww143
[Indexed for MEDLINE]
Free PMC Article

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