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

Objective We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (250HD) 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 250HD and CRP. For survival analyses, we assayed 250HD 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 17.3 nmol/L; p=3.6e-9) in plasma 250HD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 250HD was independent of CRP. In cohort analyses, 250HD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-Ill demonstrated associations between 250HD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 250HD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 250HD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81).We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 250HD with clinically useful predictive performance (area under the curve 0.77). Conclusions CRC surgery induces a fall in circulating 250HD. Plasma 250HD level is a prognostic biomarker with low 250HD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.