Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation

Xiaomeng Zhang; Yazhou He; Xue Li; Rasha Shraim; Wei Zu; Lijuan Wang; Susan M Farrington; Harry Campbell; Maria Timofeeva; Lina Zgaga; Peter Vaughan-shaw; Evropi Theodoratou; Malcolm G Dunlop

Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation

Xiaomeng Zhang, Yazhou He, Xue Li, Rasha Shraim, Wei Zu, Lijuan Wang, Susan M Farrington, Harry Campbell, Maria Timofeeva, Lina Zgaga, Peter Vaughan-shaw, Evropi Theodoratou^*, Malcolm G Dunlop^*

^*Corresponding author for this work

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

Abstract

Background
To investigate the association between circulating 25-hydroxyvitamin D (25-OHD) and colorectal cancer (CRC) survival outcomes.

Methods
We conducted analyses among the Study of Colorectal Cancer in Scotland (SOCCS) and the UK Biobank (UKBB). Both cancer-specific (CSS) and overall survival (OS) outcomes were examined. The 25-OHD levels were categorized into three groups, and multi-variable Cox-proportional hazard models were applied to estimate hazard ratios (HRs). We performed individual-level Mendelian randomisation (MR) through the generated Polygenic risk scores (PRS) of 25-OHD and summary-level MR using the inverse-variance weighted (IVW) method.

Results
We observed significantly poorer CSS (HR=0.65,95%CI=0.55-0.76,P=1.03×10-7) and OS (HR=0.66,95%CI=0.58-0.75,P=8.15×10-11) in patients with the lowest compared to those with the highest 25-OHD after adjusting for covariates. These associations remained across patients with varied tumour sites and stages. However, we found no significant association between 25-OHD PRS and either CSS (HR=0.98,95%CI=0.80-1.19,P=0.83) or OS (HR=1.07,95%CI=0.91-1.25,P=0.42). Furthermore, we found no evidence for causal effects by conducting summary-level MR analysis for either CSS (IVW:HR=1.04,95%CI=0.85-1.28,P=0.70) or OS (IVW:HR=1.10,95%CI=0.93-1.31,P=0.25).

Conclusion
This study supports the observed association between lower circulating 25-OHD and poorer survival outcomes for CRC patients. Whilst the genotype-specific association between better outcomes and higher 25-OHD is intriguing, we found no support for causality using MR approaches.

Original language	English
Journal	British Journal of Cancer
Publication status	Published - 13 Mar 2024

Keywords / Materials (for Non-textual outputs)

Vitamin D
colorectal cancer survival
PRS

Access to Document

s41416-024-02643-5-1
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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

Cite this

@article{412f5bc069f8443088824ab1b2d6be08,

title = "Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation",

abstract = "Background To investigate the association between circulating 25-hydroxyvitamin D (25-OHD) and colorectal cancer (CRC) survival outcomes.Methods We conducted analyses among the Study of Colorectal Cancer in Scotland (SOCCS) and the UK Biobank (UKBB). Both cancer-specific (CSS) and overall survival (OS) outcomes were examined. The 25-OHD levels were categorized into three groups, and multi-variable Cox-proportional hazard models were applied to estimate hazard ratios (HRs). We performed individual-level Mendelian randomisation (MR) through the generated Polygenic risk scores (PRS) of 25-OHD and summary-level MR using the inverse-variance weighted (IVW) method.ResultsWe observed significantly poorer CSS (HR=0.65,95%CI=0.55-0.76,P=1.03×10-7) and OS (HR=0.66,95%CI=0.58-0.75,P=8.15×10-11) in patients with the lowest compared to those with the highest 25-OHD after adjusting for covariates. These associations remained across patients with varied tumour sites and stages. However, we found no significant association between 25-OHD PRS and either CSS (HR=0.98,95%CI=0.80-1.19,P=0.83) or OS (HR=1.07,95%CI=0.91-1.25,P=0.42). Furthermore, we found no evidence for causal effects by conducting summary-level MR analysis for either CSS (IVW:HR=1.04,95%CI=0.85-1.28,P=0.70) or OS (IVW:HR=1.10,95%CI=0.93-1.31,P=0.25).ConclusionThis study supports the observed association between lower circulating 25-OHD and poorer survival outcomes for CRC patients. Whilst the genotype-specific association between better outcomes and higher 25-OHD is intriguing, we found no support for causality using MR approaches. ",

keywords = "Vitamin D, colorectal cancer survival, PRS",

author = "Xiaomeng Zhang and Yazhou He and Xue Li and Rasha Shraim and Wei Zu and Lijuan Wang and Farrington, {Susan M} and Harry Campbell and Maria Timofeeva and Lina Zgaga and Peter Vaughan-shaw and Evropi Theodoratou and Dunlop, {Malcolm G}",

year = "2024",

month = mar,

day = "13",

language = "English",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation

AU - Zhang, Xiaomeng

AU - He, Yazhou

AU - Li, Xue

AU - Shraim, Rasha

AU - Zu, Wei

AU - Wang, Lijuan

AU - Farrington, Susan M

AU - Campbell, Harry

AU - Timofeeva, Maria

AU - Zgaga, Lina

AU - Vaughan-shaw, Peter

AU - Theodoratou, Evropi

AU - Dunlop, Malcolm G

PY - 2024/3/13

Y1 - 2024/3/13

N2 - Background To investigate the association between circulating 25-hydroxyvitamin D (25-OHD) and colorectal cancer (CRC) survival outcomes.Methods We conducted analyses among the Study of Colorectal Cancer in Scotland (SOCCS) and the UK Biobank (UKBB). Both cancer-specific (CSS) and overall survival (OS) outcomes were examined. The 25-OHD levels were categorized into three groups, and multi-variable Cox-proportional hazard models were applied to estimate hazard ratios (HRs). We performed individual-level Mendelian randomisation (MR) through the generated Polygenic risk scores (PRS) of 25-OHD and summary-level MR using the inverse-variance weighted (IVW) method.ResultsWe observed significantly poorer CSS (HR=0.65,95%CI=0.55-0.76,P=1.03×10-7) and OS (HR=0.66,95%CI=0.58-0.75,P=8.15×10-11) in patients with the lowest compared to those with the highest 25-OHD after adjusting for covariates. These associations remained across patients with varied tumour sites and stages. However, we found no significant association between 25-OHD PRS and either CSS (HR=0.98,95%CI=0.80-1.19,P=0.83) or OS (HR=1.07,95%CI=0.91-1.25,P=0.42). Furthermore, we found no evidence for causal effects by conducting summary-level MR analysis for either CSS (IVW:HR=1.04,95%CI=0.85-1.28,P=0.70) or OS (IVW:HR=1.10,95%CI=0.93-1.31,P=0.25).ConclusionThis study supports the observed association between lower circulating 25-OHD and poorer survival outcomes for CRC patients. Whilst the genotype-specific association between better outcomes and higher 25-OHD is intriguing, we found no support for causality using MR approaches.

AB - Background To investigate the association between circulating 25-hydroxyvitamin D (25-OHD) and colorectal cancer (CRC) survival outcomes.Methods We conducted analyses among the Study of Colorectal Cancer in Scotland (SOCCS) and the UK Biobank (UKBB). Both cancer-specific (CSS) and overall survival (OS) outcomes were examined. The 25-OHD levels were categorized into three groups, and multi-variable Cox-proportional hazard models were applied to estimate hazard ratios (HRs). We performed individual-level Mendelian randomisation (MR) through the generated Polygenic risk scores (PRS) of 25-OHD and summary-level MR using the inverse-variance weighted (IVW) method.ResultsWe observed significantly poorer CSS (HR=0.65,95%CI=0.55-0.76,P=1.03×10-7) and OS (HR=0.66,95%CI=0.58-0.75,P=8.15×10-11) in patients with the lowest compared to those with the highest 25-OHD after adjusting for covariates. These associations remained across patients with varied tumour sites and stages. However, we found no significant association between 25-OHD PRS and either CSS (HR=0.98,95%CI=0.80-1.19,P=0.83) or OS (HR=1.07,95%CI=0.91-1.25,P=0.42). Furthermore, we found no evidence for causal effects by conducting summary-level MR analysis for either CSS (IVW:HR=1.04,95%CI=0.85-1.28,P=0.70) or OS (IVW:HR=1.10,95%CI=0.93-1.31,P=0.25).ConclusionThis study supports the observed association between lower circulating 25-OHD and poorer survival outcomes for CRC patients. Whilst the genotype-specific association between better outcomes and higher 25-OHD is intriguing, we found no support for causality using MR approaches.

KW - Vitamin D

KW - colorectal cancer survival

KW - PRS

M3 - Article

SN - 0007-0920

JO - British Journal of Cancer

JF - British Journal of Cancer

ER -

Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

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

Cite this