Abstract 4824: Serum vitamin D, vitamin D binding protein, and incident colorectal cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort.
Authors: Weinstein Stephanie J. , Purdue Mark P. , Smith-Warner Stephanie A. , Mondul Alison M. , Black Amanda , Horst Ronald L. , Ziegler Regina G. , Albanes Demetrius 
Published: August 2014

Many, but not all, prospective studies indicate that circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, is inversely associated with colorectal cancer risk. Importantly, any impact of vitamin D binding protein (DBP), the primary transporter of vitamin D compounds in the circulation, on the association has not been examined. Prediagnostic serum concentrations of 25(OH)D and DBP were measured in 476 incident colorectal cancer cases and 476 controls (matched on age, gender, race, and date of blood collection) from the PLCO cohort (baseline age 55-74y). We used a chemiluminescence immunoassay and a Quantikine Human DBP Immunoassay to measure 25(OH)D and DBP, with coefficients of variation of 7.8% and 14.9%, respectively. Conditional logistic regression models, adjusted for body mass index, provided odds ratios (OR) and 95% confidence intervals (CI) for the associations between both 25(OH)D and DBP concentrations and risk of colorectal cancer (no other confounders were identified). Season-specific quintiles of 25(OH)D were calculated separately based on the distribution of 25(OH)D among controls in winter/spring and summer/autumn, and combined into one quintile classification that was included in models as indicator variables; DBP was categorized as quintiles based on the distribution among controls. 25(OH)D concentrations were significantly higher among controls compared with cases [median (interquartile range): 56.5 (41.2-71.1) vs. 52.3 (39.6-64.8) nmol/L, p=0.01], while DBP did not differ by case status [3584 (2715-4938) vs. 3775 (2579-4890) nmol/L, for controls and cases, respectively; p=0.96]. DBP and 25(OH)D were positively correlated (r=0.19, p&lt;0.0001). Circulating 25(OH)D was significantly inversely associated with colorectal cancer risk (OR = 0.60, 95% CI 0.38-0.94 for highest vs. lowest quintile, p-trend 0.008); further adjustment for DBP did not change the risk estimates. Additional analyses using season-adjusted 25(OH)D in quintiles or clinically pre-defined categories gave similar results. The inverse association for serum 25(OH)D appeared stronger in women and in participants whose blood was collected during the winter/spring months. DBP was not associated with risk of colorectal cancer (OR = 0.82, 95% CI 0.54-1.26 for the highest vs. lowest quintile, p-trend=0.94), and there was no evidence of effect modification of the 25(OH)D risk association when stratified by DBP, or vice versa. For example, OR=0.54 (0.26-1.04) for highest vs. lowest quintile of 25(OH)D when DBP was below the median, and OR=0.77 (0.41-1.43) when DBP was above the median (p-interaction 0.10). The molar ratio of 25(OH)D:DBP was also nonsignificantly inversely associated with risk (p=0.06). In summary, circulating 25(OH)D was inversely associated with colorectal cancer risk, and not modified by DBP status.

Citation Format: Stephanie J. Weinstein, Mark P. Purdue, Stephanie A. Smith-Warner, Alison M. Mondul, Amanda Black, Ronald L. Horst, Regina G. Ziegler, Demetrius Albanes. Serum vitamin D, vitamin D binding protein, and incident colorectal cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4824. doi:10.1158/1538-7445.AM2013-4824