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Title: Vitamin D Metabolic Pathway Genes and Pancreatic Cancer Risk
Author: Arem, Hannah
Yu, Kai
Xiong, Xiaoqin
Moy, Kristin
Freedman, Neal D.
Mayne, Susan T.
Albanes, Demetrius
Arslan, Alan A.
Austin, Melissa
Bamlet, William R.
Beane Freeman, Laura
Bracci, Paige
Canzian, Federico
Cotterchio, Michelle
Duell, Eric J.
Gallinger, Steve
Giles, Graham G.
Goggins, Michael
Goodman, Phyllis J.
Hartge, Patricia
Hassan, Manal
Helzlsouer, Kathy
Henderson, Brian
Holly, Elizabeth A.
Hoover, Robert
Jacobs, Eric J.
Kamineni, Aruna
Klein, Alison
Klein, Eric
Kolonel, Laurence N.
Li, Donghui
Malats, Núria
Männistö, Satu
McCullough, Marjorie L.
Olson, Sara H.
Orlow, Irene
Peters, Ulrike
Petersen, Gloria M.
Porta, Miquel
Severi, Gianluca
Shu, Xiao-Ou
Visvanathan, Kala
White, Emily
Yu, Herbert
Zeleniuch-Jacquotte, Anne
Zheng, Wei
Tobias, Geoffrey S.
Maeder, Dennis
Brotzman, Michelle
Risch, Harvey
Sampson, Joshua N.
Stolzenberg-Solomon, Rachael Z.
Keywords: Càncer de pàncrees
Vitamina D
Pancreas cancer
Vitamin D
Issue Date: 23-Mar-2015
Publisher: Public Library of Science (PLoS)
Abstract: Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (<= 50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186), LRP2 (rs4668123), CYP24A1 (rs2762932), GC (rs2282679), and CUBN (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.
Note: Reproducció del document publicat a:
It is part of: PLoS One, 2015, vol. 10, num. 3, p. e0117574
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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