RT Journal Article
T1 Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations.
A1 Fedirko, Veronika
A1 Mandle, Hannah B
A1 Zhu, Wanzhe
A1 Hughes, David J
A1 Siddiq, Afshan
A1 Ferrari, Pietro
A1 Romieu, Isabelle
A1 Riboli, Elio
A1 Bueno-de-Mesquita, Bas
A1 van Duijnhoven, Fränzel J B
A1 Siersema, Peter D
A1 Tjønneland, Anne
A1 Olsen, Anja
A1 Perduca, Vittorio
A1 Carbonnel, Franck
A1 Boutron-Ruault, Marie-Christine
A1 Kühn, Tilman
A1 Johnson, Theron
A1 Krasimira, Aleksandrova
A1 Trichopoulou, Antonia
A1 Makrythanasis, Periklis
A1 Thanos, Dimitris
A1 Panico, Salvatore
A1 Krogh, Vittorio
A1 Sacerdote, Carlotta
A1 Skeie, Guri
A1 Weiderpass, Elisabete
A1 Colorado-Yohar, Sandra
A1 Sala, Núria
A1 Barricarte, Aurelio
A1 Sanchez-Perez, Maria-Jose
A1 Quirós, Ramón
A1 Amiano, Pilar
A1 Gylling, Björn
A1 Harlid, Sophia
A1 Perez-Cornago, Aurora
A1 Heath, Alicia K
A1 Tsilidis, Konstantinos K
A1 Aune, Dagfinn
A1 Freisling, Heinz
A1 Murphy, Neil
A1 Gunter, Marc J
A1 Jenab, Mazda
K1 colorectal neoplasms
K1 incidence
K1 single nucleotide polymorphism (SNP)
K1 vitamin D
AB 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.
PB MDPI AG
YR 2019
FD 2019-08-12
LK http://hdl.handle.net/10668/14423
UL http://hdl.handle.net/10668/14423
LA en
NO Fedirko V, Mandle HB, Zhu W, Hughes DJ, Siddiq A, Ferrari P, el al. Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations. Nutrients. 2019 Aug 20;11(8):1954.
NO Funding for this particular study was obtained from Wereld Kanker Onderzoek Fonds (WKOF) [Grant Number WCRF 2011-443; PI: M. Jenab], as part of the World Cancer Research Fund International grant programme. The EPIC study was supported by “Europe Against Cancer” Programme of the European Commission (SANCO); Ligue contre le Cancer; Institut Gustave Roussy; Mutuelle Générale de l’Education Nationale; Institut National de la Santé et de la Recherche Médicale (INSERM); German Cancer Aid; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; the CIBER en Epidemiología y Salud Pública (CIBERESP), Spain; ISCIII RETIC (RD06/0020); Spanish Regional Governments of Andalusia, Asturias, Basque Country, Murcia (No 6236) and Navarra and the Catalan Institute of Oncology; Cancer Research UK; Medical Research Council, UK; The Hellenic Health Foundation; Italian Association for Research on Cancer; Italian National Research Council; Compagnia di San Paolo; Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Swedish Cancer Society; Swedish Scientific Council; Regional Governments of Skane and Vasterbotten, Sweden; and Nordforsk centre of excellence programme HELGA. Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 for EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). DJH was supported by the Health Research Board of Ireland health research award HRA-PHS-2015-1142.
DS RISalud
RD Apr 10, 2025