Nutrients (Aug 2019)
Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
- Veronika Fedirko,
- Hannah B. Mandle,
- Wanzhe Zhu,
- David J. Hughes,
- Afshan Siddiq,
- Pietro Ferrari,
- Isabelle Romieu,
- Elio Riboli,
- Bas Bueno-de-Mesquita,
- Fränzel J.B. van Duijnhoven,
- Peter D. Siersema,
- Anne Tjønneland,
- Anja Olsen,
- Vittorio Perduca,
- Franck Carbonnel,
- Marie-Christine Boutron-Ruault,
- Tilman Kühn,
- Theron Johnson,
- Aleksandrova Krasimira,
- Antonia Trichopoulou,
- Periklis Makrythanasis,
- Dimitris Thanos,
- Salvatore Panico,
- Vittorio Krogh,
- Carlotta Sacerdote,
- Guri Skeie,
- Elisabete Weiderpass,
- Sandra Colorado-Yohar,
- Núria Sala,
- Aurelio Barricarte,
- Maria-Jose Sanchez,
- Ramón Quirós,
- Pilar Amiano,
- Björn Gylling,
- Sophia Harlid,
- Aurora Perez-Cornago,
- Alicia K. Heath,
- Konstantinos K. Tsilidis,
- Dagfinn Aune,
- Heinz Freisling,
- Neil Murphy,
- Marc J. Gunter,
- Mazda Jenab
Affiliations
- Veronika Fedirko
- Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
- Hannah B. Mandle
- Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
- Wanzhe Zhu
- Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
- David J. Hughes
- Cancer Biology and Therapeutics Group (CBT), Conway Institute, School of Biomolecular and Biomedical Science (SBBS), University College Dublin, Dublin, Ireland
- Afshan Siddiq
- Genomics England, London EC1M 6BQ, UK
- Pietro Ferrari
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon 69372, France
- Isabelle Romieu
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon 69372, France
- Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2AZ, UK
- Bas Bueno-de-Mesquita
- Division of Human Nutrition & Health, Wageningen University & Research, 6700 AA Wageningen, The Netherlands
- Fränzel J.B. van Duijnhoven
- Division of Human Nutrition & Health, Wageningen University & Research, 6700 AA Wageningen, The Netherlands
- Peter D. Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
- Anne Tjønneland
- Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
- Anja Olsen
- Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
- Vittorio Perduca
- Laboratoire de Mathématiques Appliquées MAP5, Université Paris Descartes, 75006 Paris, France
- Franck Carbonnel
- CESP, Fac. de médecine—Univ. Paris-Sud, Fac. de médecine—UVSQ, INSERM, Université Paris-Saclay, F-94805 Villejuif, France
- Marie-Christine Boutron-Ruault
- CESP, Fac. de médecine—Univ. Paris-Sud, Fac. de médecine—UVSQ, INSERM, Université Paris-Saclay, F-94805 Villejuif, France
- Tilman Kühn
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Theron Johnson
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Aleksandrova Krasimira
- Nutrition, Immunity and Metabolism, Department of Epidemiology, German Institute for Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert Allee, 14558 Nuthetal, Germany
- Antonia Trichopoulou
- Hellenic Health Foundation, 115 27 Athens, Greece
- Periklis Makrythanasis
- Hellenic Health Foundation, 115 27 Athens, Greece
- Dimitris Thanos
- Hellenic Health Foundation, 115 27 Athens, Greece
- Salvatore Panico
- Dipartimento Di Medicina Clinica E Chirurgia, Federico Ii University, 80138 Naples, Italy
- Vittorio Krogh
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 20133 Milano, Italy
- Carlotta Sacerdote
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), 10126 Turin, Italy
- Guri Skeie
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway
- Elisabete Weiderpass
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway
- Sandra Colorado-Yohar
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia 30008, Spain
- Núria Sala
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, and Translational Research Laboratory, Catalan Institute of Oncology (ICO)-IDIBELL, 08908 Barcelona, Spain
- Aurelio Barricarte
- CIBER Epidemiology and Public Healh (CIBERESP), Madrid 28029, Spain
- Maria-Jose Sanchez
- CIBER Epidemiology and Public Healh (CIBERESP), Madrid 28029, Spain
- Ramón Quirós
- Public Health Directorate, Asturias 33006, Spain
- Pilar Amiano
- CIBER Epidemiology and Public Healh (CIBERESP), Madrid 28029, Spain
- Björn Gylling
- Department of Medical Biosciences, Pathology, Umeå University, 901 87 Umeå, Sweden
- Sophia Harlid
- Department of Radiation Sciences, Oncology, Umeå University, 901 87 Umeå, Sweden
- Aurora Perez-Cornago
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK
- Alicia K. Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2AZ, UK
- Konstantinos K. Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2AZ, UK
- Dagfinn Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2AZ, UK
- Heinz Freisling
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon 69372, France
- Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon 69372, France
- Marc J. Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon 69372, France
- Mazda Jenab
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon 69372, France
- DOI
- https://doi.org/10.3390/nu11081954
- Journal volume & issue
-
Vol. 11,
no. 8
p. 1954
Abstract
Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini–Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.
Keywords