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Colorectal Cancer risk increases when genes reduce the vitamin D levels – Aug 2019

Nutrients. 2019 Aug 20;11(8). pii: E1954. doi: 10.3390/nu11081954.

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Study looks at many genes - here is a portion on the Vitamin D Receptor
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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.

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  • Another “study found a statistically significant 4-fold increase in the enrichment of VDR binding sites located in genes associated with CRC, and a 3.5-fold increase in enrichment located in genes associated with Crohn’s disease [19]
Created by admin. Last Modification: Friday August 23, 2019 11:58:44 GMT-0000 by admin. (Version 7)

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ID Name Comment Uploaded Size Downloads
12533 CRC VDR.jpg admin 23 Aug, 2019 11:45 27.33 Kb 30
12532 CRC 10 vitamin D genes.jpg admin 23 Aug, 2019 11:45 83.60 Kb 42
12531 CRC vitamin D genes.pdf PDF 2019 admin 23 Aug, 2019 11:45 366.31 Kb 8
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