Vitamin D metabolic pathway genes and pancreatic cancer risk.

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.

• Authors: Hannah Arem, Kai Yu, Xiaoqin Xiong, Kristin Moy, Neal D Freedman, Susan T Mayne, Demetrius Albanes, Alan A Arslan, Melissa Austin, William R Bamlet, Laura Beane-Freeman, Paige Bracci, Federico Canzian, Michelle Cotterchio, Eric J Duell, Steve Gallinger, Graham G Giles, Michael Goggins, Phyllis J Goodman, Patricia Hartge, Manal Hassan, Kathy Helzlsouer, Brian Henderson, Elizabeth A Holly, Robert Hoover, Eric J Jacobs, Aruna Kamineni, Alison Klein, Eric Klein, Laurence N Kolonel, Donghui Li, Núria Malats, Satu Männistö, Marjorie L McCullough, Sara H Olson, Irene Orlow, Ulrike Peters, Gloria M Petersen, Miquel Porta, Gianluca Severi, Xiao-Ou Shu, Kala Visvanathan, Emily White, Herbert Yu, Anne Zeleniuch-Jacquotte, Wei Zheng, Geoffrey S Tobias, Dennis Maeder, Michelle Brotzman, Harvey Risch, Joshua N Sampson, Rachael Z Stolzenberg-Solomon
• Journal: PloS one (PLoS One) Vol. 10 Issue 3 Pg. e0117574 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25799011 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor
• Vitamin D-Binding Protein
• Vitamins
• Vitamin D

Topics

• Biomarkers, Tumor (genetics)
• Case-Control Studies
• Cohort Studies
• Follow-Up Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Metabolic Networks and Pathways (genetics)
• Pancreatic Neoplasms (blood, genetics)
• Polymorphism, Single Nucleotide (genetics)
• Risk Factors
• Vitamin D (blood, genetics)
• Vitamin D-Binding Protein (genetics)
• Vitamins (blood, genetics)