Vitamin D-related genes, blood vitamin D levels and colorectal cancer risk in western european populations
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 366 KB, PDF-dokument
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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 1954 |
| Tidsskrift | Nutrients |
| Vol/bind | 11 |
| Udgave nummer | 8 |
| ISSN | 2072-6643 |
| DOI | |
| Status | Udgivet - 2019 |
| Eksternt udgivet | Ja |
Bibliografisk note
Funding Information:
Funding for this particular study was obtained from Wereld Kanker Onderzoek Fonds (WKOF) [Grant Number WCRF 2011-443; PI: M. Jenab], as part of theWorld 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 G?n?rale de l?Education Nationale; Institut National de la Sant? et de la Recherche M?dicale (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 Epidemiolog?a y Salud P?blica (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.
Funding Information:
Funding: 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.
Publisher Copyright:
© 2019 by the authors.
ID: 290601142