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PLoS One. 2015 Mar 23;10(3):e0117574. doi: 10.1371/journal.pone.0117574. eCollection 2015.

Vitamin D metabolic pathway genes and pancreatic cancer risk.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
2
Information Management Systems, Inc., Calverton, Maryland, United States of America.
3
Yale School of Public Health/Yale Cancer Center, New Haven, Connecticut, United States of America.
4
Departments of Population Health, Obstetrics and Gynecology (Obs/Gyn) and Environmental Medicine, New York University, New York, New York, United States of America.
5
Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
6
Department of Epidemiology, Mayo Clinic, Rochester, Minnesota, United States of America.
7
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
8
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
9
Dalla Lana School of Public Health, University of Toronto; Prevention and Cancer Control, Cancer Care Ontario Toronto, Ontario, Canada.
10
Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
11
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
12
Cancer Epidemiology Centre, Cancer Council Victoria and Centre for MEGA Epidemiology, School of Population Health, the University of Melbourne, Melbourne, Australia.
13
Departments of Oncology, Pathology and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
14
Cleveland Clinic, Glickman Urological and Kidney Institute, Cleveland, Ohio, United States of America.
15
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
16
MD Mercy, Baltimore, Maryland, United States of America.
17
Department of Preventative Medicine, School of Medicine, University of Southern California, Los Angeles, California, United States of America.
18
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America.
19
GroupHealth Research Institute, Seattle, Washington, United States of America.
20
University of Hawaii Cancer Center, Manoa, Hawaii, United States of America.
21
Molecular Pathology Program, Spanish National Cancer Research Center, Madrid, Spain.
22
National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland.
23
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
24
Hospital del Mar Institute of Medical Research (IMIM), and School of Medicine, Barcelona Spain.
25
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, United States of America.
26
Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
27
Westat, Rockville, Maryland, United States of America.

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.

PMID:
25799011
PMCID:
PMC4370655
DOI:
10.1371/journal.pone.0117574
[Indexed for MEDLINE]
Free PMC Article

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