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
Year: 2016
Type: article
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.
Source: American Journal of Epidemiology
DOI: 10.1093/aje/kww143
Authors: Vasiliki I. Dimitrakopoulou, Ruth C. Travis, Irene M. Shui, Alison Mondul, Demetrius Albanes, Jarmo Virtamo, Antonio Agudo, Heiner Boeing, H. Bas Bueno-de-Mesquita, Marc J. Gunter, Mattias Johansson, Kay-Tee Khaw, Kim Overvad, Domenico Palli, Antonia Trichopoulou, Edward Giovannucci, David J. Hunter, Sara Lindström, Walter Willett, J. Michael Gaziano, Meir Stampfer, Christine Berg, Sonja I. Berndt, Amanda Black, Robert N. Hoover, Peter Kraft, Timothy J. Key, Konstantinos K. Tsilidis
Institutions: University of Ioannina, University of Oxford, Harvard University, Fred Hutch Cancer Center, University of Michigan, National Institutes of Health, Division of Cancer Epidemiology and Genetics, Finnish Institute for Health and Welfare, Institut Català d'Oncologia, German Institute of Human Nutrition, University of Malaya, National Institute for Public Health and the Environment, Imperial College London, Centre international de recherche sur le cancer, Swedish University of Agricultural Sciences, University of Cambridge, Aarhus University, Aalborg University Hospital, Istituto per lo Studio e la Prevenzione Oncologica, Hellenic Health Foundation, Brigham and Women's Hospital, The University of Sydney, Royal North Shore Hospital, University of Washington, VA Boston Healthcare System, University of Bonn, Rush University Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Defense, World Health Organization, Brigham and Women's Hospital, Division of Cancer Prevention, National Cancer Institute, Aarhus Universitet, Kræftens Bekæmpelse, Harvard T.H. Chan School of Public Health, Deutsches Krebsforschungszentrum, Centre International de Recherche sur le Cancer, School of Public Health, University of Michigan, Cancer Research UK, National Institute for Health and Care Research, Imperial College London, University of Oxford, European Commission, University College Dublin, Bundesministerium für Bildung und Forschung, Cancerfonden, Vetenskapsrådet, Universiti Malaya, Umeå Universitet, Associazione Italiana per la Ricerca sul Cancro, National and Kapodistrian University of Athens, Deutsche Krebshilfe, Terveyden ja hyvinvoinnin laitos, Hellenic Health Foundation, University of Ioannina, National Institutes of Health, Medical Research Council, World Cancer Research Fund, Instituto de Salud Carlos III, Health and Medical Research Fund, European Regional Development Fund, Medicinska fakulteten, Umeå Universitet, School of Public Health, Imperial College London, National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Awards: G1032970344, G1055973116, G1075502044, G1148307873, G1192877484, G1208621354, G1364610698, G1420790711, G1478484880, G1559294051, G172151099, G1767199718, G1788645866, G1926550620, G1993546569, G2027148636, G2036036603, G2072618322, G2092716656, G2149865848, G2235605558, G2336049343, G2539064604, G2561548287, G2611591051, G2642285025, G2663613759, G268454541, G2736363316, G2841678936, G2871896171, G2919159421, G2933204024, G2999139090, G3010599472, G3077395769, G3084320185, G3189789075, G3276551827, G331404038, G3350062835, G3452641779, G3675143906, G375319704, G395156118, G3980646122, G4015216323, G4041385912, G4063614301, G4089957676, G4187108342, G4213141252, G4305317257, G4682079261, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G4857818444, G4884057766, G4913827001, G4996234081, G5004963360, G5021959070, G5034473772, G5119219000, G5375816427, G5651954792, G569447510, G569908600, G5706284561, G5750710683, G5897142711, G589878898, G5990830295, G6022976577, NIHR Senior Investigator Award, G6212483348, G6238616637, G6305665937, G639206035, G6486574503, G6570774229, G657255654, G6594529311, G6723261869, G6779186093, G6820515600, G6868151656, G6960682749, G7020115967, G7040807446, G7271584288, G7306252069, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G7447125227, G7600088736, G7624991799, G7646326732, G7838322234, G7853538257, G7983476435, G7993655663, G8013581208, G8050896463, G8147327976, G817390530, G8331243404, G8374761964, G8407261631, G8500560359, G8508326818, G8716998914, G8813442493, G8867963557, G8869854444, G8978728421, G9000332718, G970870506
OpenAlex ID: W2589459138