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Impact of Circulating Vitamin D Binding Protein Levels on the Association between 25-Hydroxyvitamin D and Pancreatic Cancer Risk: A Nested Case-Control Study

  1. Author:
    Weinstein, S. J.
    Stolzenberg-Solomon, R. Z.
    Kopp, W.
    Rager, H.
    Virtamo, J.
    Albanes, D.

  2. Author Address

    [Weinstein, Stephanie J.; Stolzenberg-Solomon, Rachael Z.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20982 USA. [Kopp, William; Rager, Helen] SAIC Frederick Inc, NCI Frederick, Clin Support Lab, Frederick, MD USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Albanes, D (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Executive Blvd,Suite 320, Bethesda, MD 20982 USA;daa@nih.gov
    1. Year: 2012
    2. Date: Mar
  2. Journal: Cancer Research
    1. 72
    2. 5
    3. Pages: 1190-1198
  4. Type of Article: Article
  5. ISSN: 0008-5472
  1. Abstract:

    High concentrations of circulating 25-hydroxyvitamin D [25(OH)D] have been associated with elevated pancreatic cancer risk. As this is contrary to an expected inverse association between vitamin D status and cancer, we examined whether vitamin D binding protein (DBP), the primary carrier of vitamin D compounds in circulation, plays a role in this relationship. Prediagnostic serum DBP and 25(OH)D were studied in relation to risk of pancreatic cancer in a nested case-control study of 234 cases and 234 controls in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. ORs and 95% CIs were estimated using logistic regression, and statistical tests were two-sided. We found that DBP and 25(OH)D were correlated (r = 0.27, P < 0.0001), and DBP was inversely associated with pancreatic cancer risk (OR = 0.66, 95% CI = 0.39-1.12, for the highest vs. lowest quartile; P-trend = 0.02). Importantly, this association seemed to have a threshold between quartiles 2 to 4 and quartile 1, and was primarily evident among men with concurrent high 25(OH)D concentrations (OR = 0.33, 95% CI = 0.16-0.70 for highest vs. lowest quartile; P-trend = 0.002), with no association in men with lower serum 25(OH) D (OR 1.28, 95% CI = 0.62-2.61 for highest vs. lowest quartile, P-trend 0.63, P-interaction = 0.01). Men with higher 25(OH) D concentrations and serum DBP below the median showed greatly elevated risk of pancreatic cancer (OR = 5.01, 95% CI 2.33-10.78, for highest vs. lowest quartile; P-trend < 0.0001), while risk was weakly inversely associated with serum 25(OH) D when DBP concentrations were higher (P-interaction = 0.001). Taken together, our findings indicate that higher DBP concentrations may sequester more 25(OH) D and reduce free 25(OH) D bioavailability. Simultaneous examination of DBP and 25(OH) D may be important in determining the association of vitamin D with cancer risk. Cancer Res; 72(5); 1190-8. (C) 2012 AACR.

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External Sources

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  2. DOI: 10.1158/0008-5472.can-11-2950
  3. View record in Web of Science®
  4. WOS: 000300989100018

Library Notes

  1. Fiscal Year: FY2011-2012
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