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

P G Vaughan-Shaw; L Zgaga; L Y Ooi; E Theodoratou; M Timofeeva; V. Svinti; Marion Walker; F O'Sullivan; A Ewing; S Johnston; F V N Din; H Campbell; S M Farrington; M G Dunlop

doi:10.1136/gutjnl-2018-317922

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

P G Vaughan-Shaw, L Zgaga, L Y Ooi, E Theodoratou, M Timofeeva, V. Svinti, Marion Walker, F O'Sullivan, A Ewing, S Johnston, F V N Din, H Campbell, S M Farrington, M G Dunlop

Research output: Contribution to journal › Article › peer-review

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 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1–2). CRP peaked 3–5 days postoperatively (143.1 mg/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=48.8 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–III demonstrated associations between 25OHD 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 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 to 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 (area under the curve 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.

Original language	English
Pages (from-to)	103-111
Number of pages	9
Journal	Gut
Volume	69
Issue number	1
Early online date	25 Apr 2019
DOIs	https://doi.org/10.1136/gutjnl-2018-317922
Publication status	Published - Jan 2020

Keywords / Materials (for Non-textual outputs)

25-hydroxyvitamin D,
CRP
vitamin D
colon
surgery

Access to Document

10.1136/gutjnl-2018-317922Licence: Creative Commons: Attribution (CC-BY)

Low_plasma_vitamin_D_is_associated_with_adverse_colorectal cancer survivalFinal published version, 831 KBLicence: Creative Commons: Attribution (CC-BY)

MC_UU_00007/1 Genetic approaches to combating colorectal cancer
Dunlop, M. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research
Colorectal cancer reduction through risk stratification of screening, follow-up and treatment
Theodoratou, E. (Principal Investigator)
UK-based charities
1/05/17 → 30/04/23
Project: Research
Integrative Genomics in Colorectal Cancer Susceptibility:Developing risk reducing interventions through understanding biology
Dunlop, M. (Principal Investigator), Campbell, H. (Co-investigator), Farrington, S. (Co-investigator) & Theodoratou, E. (Co-investigator)
UK-based charities
1/01/16 → 31/05/21
Project: Research

Susan Farrington
- Edinburgh Cancer Research Centre
- School of Genetics and Cancer - Personal Chair of Colorectal Cancer Genetics
Person: Academic: Research Active

Cite this

Vaughan-Shaw, P. G., Zgaga, L., Ooi, L. Y., Theodoratou, E., Timofeeva, M., Svinti, V., Walker, M., O'Sullivan, F., Ewing, A., Johnston, S., Din, F. V. N., Campbell, H., Farrington, S. M., & Dunlop, M. G. (2020). Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response. Gut, 69(1), 103-111. https://doi.org/10.1136/gutjnl-2018-317922

@article{cc1db478124640bc9c7240fb810bace4,

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

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 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1–2). CRP peaked 3–5 days postoperatively (143.1 mg/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=48.8 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–III demonstrated associations between 25OHD 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 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 to 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 (area under the curve 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.",

keywords = "25-hydroxyvitamin D,, CRP, vitamin D, colon, surgery",

author = "Vaughan-Shaw, {P G} and L Zgaga and Ooi, {L Y} and E Theodoratou and M Timofeeva and V. Svinti and Marion Walker and F O'Sullivan and A Ewing and S Johnston and Din, {F V N} and H Campbell and Farrington, {S M} and Dunlop, {M G}",

year = "2020",

month = jan,

doi = "10.1136/gutjnl-2018-317922",

language = "English",

volume = "69",

pages = "103--111",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

number = "1",

}

Vaughan-Shaw, PG, Zgaga, L, Ooi, LY, Theodoratou, E, Timofeeva, M, Svinti, V, Walker, M, O'Sullivan, F, Ewing, A, Johnston, S, Din, FVN , Campbell, H , Farrington, SM & Dunlop, MG 2020, 'Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response', Gut, vol. 69, no. 1, pp. 103-111. https://doi.org/10.1136/gutjnl-2018-317922

TY - JOUR

T1 - Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response

AU - Vaughan-Shaw, P G

AU - Zgaga, L

AU - Ooi, L Y

AU - Theodoratou, E

AU - Timofeeva, M

AU - Svinti, V.

AU - Walker, Marion

AU - O'Sullivan, F

AU - Ewing, A

AU - Johnston, S

AU - Din, F V N

AU - Campbell, H

AU - Farrington, S M

AU - Dunlop, M G

PY - 2020/1

Y1 - 2020/1

N2 - 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 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1–2). CRP peaked 3–5 days postoperatively (143.1 mg/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=48.8 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–III demonstrated associations between 25OHD 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 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 to 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 (area under the curve 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.

AB - 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 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1–2). CRP peaked 3–5 days postoperatively (143.1 mg/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=48.8 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–III demonstrated associations between 25OHD 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 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 to 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 (area under the curve 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.

KW - 25-hydroxyvitamin D,

KW - CRP

KW - vitamin D

KW - colon

KW - surgery

U2 - 10.1136/gutjnl-2018-317922

DO - 10.1136/gutjnl-2018-317922

M3 - Article

SN - 0017-5749

VL - 69

SP - 103

EP - 111

JO - Gut

JF - Gut

IS - 1

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

MC_UU_00007/1 Genetic approaches to combating colorectal cancer

Colorectal cancer reduction through risk stratification of screening, follow-up and treatment

Integrative Genomics in Colorectal Cancer Susceptibility:Developing risk reducing interventions through understanding biology

Profiles

Susan Farrington

Cite this