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 journalArticlepeer-review

Abstract / Description of output

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 languageEnglish
JournalBritish Journal of Cancer
Publication statusPublished - 13 Mar 2024

Keywords / Materials (for Non-textual outputs)

  • Vitamin D
  • colorectal cancer survival
  • PRS

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