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Title: Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
Author: Fedirko, Veronika
Mandle, Hannah B.
Zhu, Wanzhe
Hughes, David J.
Siddiq, Afshan
Ferrari, Pietro
Romieu, Isabelle
Riboli, Elio
Bueno de Mesquita, H. Bas
van Duijnhoven, Franzel J. B.
Siersema, Peter D.
Tjønneland, Anne
Olsen, Anja
Perduca, Vittorio
Carbonnel, Franck
Boutron-Ruault, Marie-Christine
Kühn, Tilman
Johnson, Theron
Krasimira, Aleksandrova
Trichopoulou, Antonia
Makrythanasis, Periklis
Thanos, Dimitris
Panico, Salvatore
Krogh, Vittorio
Sacerdote, Carlotta
Skeie, Guri
Weiderpass, Elisabete
Colorado Yohar, Sandra
Sala Serra, Núria
Barricarte, Aurelio
Sánchez, Maria José
Quirós, J. Ramón
Amiano, Pilar
Gylling, Björn
Harlid, Sophia
Pérez Cornago, Aurora
Heath, Alicia K.
Tsilidis, Konstantinos K.
Aune, Dagfinn
Freisling, Heinz
Murphy, Neil
Gunter, Marc J.
Jenab, Mazda
Keywords: Càncer colorectal
Vitamina D
Colorectal cancer
Vitamin D
Issue Date: 1-Aug-2019
Publisher: MDPI
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 beta (TGF beta) signaling was associated with CRC risk (P <= 0.001), with most statistically significant genes being SMAD7 (P-BH = 0.008) and SMAD3 (P-BH = 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.
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It is part of: Nutrients, 2019, vol. 11, num. 8, p. 1954
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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