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000144642 1001_ $$00000-0002-7805-9913$$aFedirko, Veronika$$b0
000144642 245__ $$aVitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations.
000144642 260__ $$aBasel$$bMDPI$$c2019
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000144642 520__ $$aHigher 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.
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000144642 7001_ $$00000-0002-0277-9607$$aMandle, Hannah B$$b1
000144642 7001_ $$aZhu, Wanzhe$$b2
000144642 7001_ $$00000-0003-1668-8770$$aHughes, David J$$b3
000144642 7001_ $$aSiddiq, Afshan$$b4
000144642 7001_ $$aFerrari, Pietro$$b5
000144642 7001_ $$aRomieu, Isabelle$$b6
000144642 7001_ $$aRiboli, Elio$$b7
000144642 7001_ $$aBueno-de-Mesquita, Bas$$b8
000144642 7001_ $$avan Duijnhoven, Fränzel J B$$b9
000144642 7001_ $$aSiersema, Peter D$$b10
000144642 7001_ $$aTjønneland, Anne$$b11
000144642 7001_ $$00000-0003-4788-503X$$aOlsen, Anja$$b12
000144642 7001_ $$00000-0003-0339-0473$$aPerduca, Vittorio$$b13
000144642 7001_ $$aCarbonnel, Franck$$b14
000144642 7001_ $$aBoutron-Ruault, Marie-Christine$$b15
000144642 7001_ $$0P:(DE-He78)0907a10ba1dc8f53f04907f54f6fdcfe$$aKühn, Tilman$$b16$$udkfz
000144642 7001_ $$0P:(DE-He78)79ab945544e5bc017a2317b6146ed3aa$$aJohnson, Theron$$b17$$udkfz
000144642 7001_ $$aKrasimira, Aleksandrova$$b18
000144642 7001_ $$aTrichopoulou, Antonia$$b19
000144642 7001_ $$aMakrythanasis, Periklis$$b20
000144642 7001_ $$aThanos, Dimitris$$b21
000144642 7001_ $$aPanico, Salvatore$$b22
000144642 7001_ $$00000-0003-0122-8624$$aKrogh, Vittorio$$b23
000144642 7001_ $$00000-0002-8008-5096$$aSacerdote, Carlotta$$b24
000144642 7001_ $$aSkeie, Guri$$b25
000144642 7001_ $$aWeiderpass, Elisabete$$b26
000144642 7001_ $$aColorado-Yohar, Sandra$$b27
000144642 7001_ $$aSala, Núria$$b28
000144642 7001_ $$aBarricarte, Aurelio$$b29
000144642 7001_ $$aSanchez, Maria-Jose$$b30
000144642 7001_ $$aQuirós, Ramón$$b31
000144642 7001_ $$aAmiano, Pilar$$b32
000144642 7001_ $$aGylling, Björn$$b33
000144642 7001_ $$aHarlid, Sophia$$b34
000144642 7001_ $$aPerez-Cornago, Aurora$$b35
000144642 7001_ $$aHeath, Alicia K$$b36
000144642 7001_ $$aTsilidis, Konstantinos K$$b37
000144642 7001_ $$aDagfinn, Aune$$b38
000144642 7001_ $$00000-0001-8648-4998$$aFreisling, Heinz$$b39
000144642 7001_ $$aMurphy, Neil$$b40
000144642 7001_ $$aGunter, Marc J$$b41
000144642 7001_ $$aJenab, Mazda$$b42
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