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Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response.

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Abstract

Objective
We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-Reactive Protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival.
Design
We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response.
Results
Serial sampling revealed a postoperative fall (mean 17.3nmol/l; P=3.6e-9) in plasma 25OHD (nadir day 1-2). CRP peaked 3-5 days postoperatively (143.1mg/l; P=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12-months following operation (mean=48.8nmol/l) than preoperatively (54.8nmol/l; P=1.2e-5) recovering after
24-months (52.2nmol/l; P=0.002). Survival analysis in AJCC stage I-III demonstrated associations between 25OHD tertile and CRC-mortality (HR=0.69; 95%CI,0.46-0.91); and all-cause mortality (HR=0.68; 95%CI,0.50-0.85) and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong
protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95%CI,0.21-0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically-useful predictive performance (AUC 0.77).
Conclusions
CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype.A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.

    Research areas

  • 25-hydroxyvitamin D, CRP, vitamin D, colon, surgery

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