☆ 4.8 Article

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

CANCER RESEARCH (2012)

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CANCER RESEARCH

卷 72, 期 5, 页码 1190-1198

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AMER ASSOC CANCER RESEARCH

DOI: 10.1158/0008-5472.CAN-11-2950

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Oncology

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National Cancer Institute (NCI) at the NIH
U.S. Public Health Service, NCI, NIH [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C, HHSN261200800001E]

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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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Association of blood lead level with vitamin D binding protein, total and free 25-hydroxyvitamin D levels in middle-school children

Abdur Rahman, Reem Al-Sabah, Reem Jallad, Muddanna S. Rao

Summary: The study found a positive association between blood lead levels and vitamin D binding protein, a non-significant negative association with total 25-hydroxyvitamin D when continuous and significant when quartiles were used, and a significant negative association with free 25-hydroxyvitamin D. Higher lead levels were associated with an increased risk of vitamin D insufficiency and deficiency. Future studies should consider the levels of vitamin D binding protein when assessing the association between lead and vitamin D metabolites.

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