Christina C. Dahm

Association of pre-diagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D-binding protein isoforms

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • David Corley Gibbs, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States
  • Roberd M Bostick, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA., Emory University, United States
  • Marjorie McCullough, Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
  • ,
  • Caroline Um, Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia., United States
  • Dana Flanders, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
  • ,
  • Mazda Jenab, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France., France
  • Elisabete Weiderpass, Director, IARC-WHO, Lyon, France.
  • ,
  • Björn Gylling, Department of Medical Biosciences, Pathology, Umea University, Umea, Sweden., Sweden
  • Inger T Gram, Department of Community Medicine, Faculty of Health Sciences, UiT The Artic University of Tromsø, Tromsø, Norway., Norway
  • Alicia K Heath, Imperial College, London, United Kingdom
  • Sandra Colorado-Yohar, Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia., Murcia Regional Health Council, CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain., Colombia
  • Christina C Dahm
  • Bas Bueno-de-Mesquita, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands., Netherlands
  • Aurora Perez-Cornago, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., United Kingdom
  • Antonia Trichopoulou, Hellenic Health Foundation, Athens, Greece., Greece
  • Rosario Tumino, Cancer Registry and Histopathology Department , Provincial Health Authority (ASP), Ragusa, Italy., Italy
  • Tilman Kühn, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. r.kaaks@dkfz-heidelberg.de., Germany
  • Veronika Fedirko, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA., Emory University, United States

Lower prediagnostic circulating 25-hydroxyvitamin D (25[OH]D)—considered the best marker of total vitamin D exposure—is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D-binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D-mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study-II) and Europe (European Prospective Investigation into Cancer and Nutrition). 25(OH)D measurements were calibrated to a single assay, season standardized, and categorized using Institute of Medicine recommendations (deficient [<30], insufficient [30 - <50], sufficient [≥50 nmol/L]). In the pooled analysis, multivariable-adjusted hazard ratios (HRs) for CRC-specific mortality associated with deficient relative to sufficient 25(OH)D concentrations were 2.24 (95% CI 1.44-3.49) among cases with the Gc2 isoform, and 0.94 (95% CI 0.68-1.22) among cases without Gc2 (P interaction =.0002). The corresponding HRs for all-cause mortality were 1.80 (95% CI 1.24-2.60) among those with Gc2, and 1.12 (95% CI 0.84-1.51) among those without Gc2 (P interaction =.004). Our findings suggest that the association of prediagnostic vitamin D status with mortality among CRC patients may differ by functional GC isoforms, and patients who inherit the Gc2 isoform (GC rs4588*A) may particularly benefit from higher circulating 25(OH)D for improved CRC prognosis.

Original languageEnglish
JournalInternational Journal of Cancer
Volume147
Issue10
Number of pages10
ISSN0020-7136
DOIs
Publication statusPublished - Nov 2020

    Research areas

  • 25-hydroxyvitamin D, cohort studies, gene-environment interaction, single nucleotide polymorphism, survival analysis, SURVIVAL, VARIANTS, 25-HYDROXYVITAMIN D, PREVENTION, SERUM, SUPPLEMENTATION, COHORT, D-RECEPTOR, GC, GENOME-WIDE ASSOCIATION

See relations at Aarhus University Citationformats

ID: 187079924