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Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study

Gibbs DC 1 , Song M 2 , McCullough ML 3 , Um CY 3 , Bostick RM 1 , Wu K 2 Show all authors , Flanders WD 1 , Giovannucci E 2 , Jenab M 4 , Brustad M 5 , Tjønneland A 6 , Perez-Cornago A 7 , Trichopoulou A 8 , Tsilidis KK 9 , Hultdin J 10 , Barricarte Gurrea A 11 , Bueno-de-Mesquita B 12 , Mahamat-Saleh Y 13 , Kühn T 14 , Gunter MJ 4 , Weiderpass E 15 , Fedirko V 1

Affiliations 

  • 1 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
  • 2 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
  • 3 Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA
  • 4 Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
  • 5 Department of Community Medicine, The Arctic University of Norway, Tromsø, Norway
  • 6 Danish Cancer Society Research Center, Copenhagen, Denmark
  • 7 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • 8 Hellenic Health Foundation, Athens, Greece
  • 9 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  • 10 Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
  • 11 Navarra Public Health Institute, Pamplona, Spain
  • 12 Former Senior Scientist, Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
  • 13 CESP, Faculty de médecine, University of Paris-Sud, Fac. de Médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif, France
  • 14 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 15 International Agency for Research on Cancer, Lyon, France
JNCI Cancer Spectr, 2020 Feb;4(1):pkz083.
PMID: 32337495 DOI: 10.1093/jncics/pkz083

Abstract

BACKGROUND: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.

METHODS: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.

RESULTS: The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, P trend = 1.2 × 10-8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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