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

Br J Cancer. 2024 May;130(9):1585-1591. doi: 10.1038/s41416-024-02643-5. Epub 2024 Mar 13.

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 survival (CSS) and overall survival (OS) outcomes were examined. The 25-OHD levels were categorised 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Colorectal Neoplasms* / blood
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / mortality
  • Colorectal Neoplasms* / pathology
  • Female
  • Humans
  • Male
  • Mendelian Randomization Analysis*
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Scotland / epidemiology
  • Vitamin D* / analogs & derivatives*
  • Vitamin D* / blood

Substances

  • Vitamin D
  • 25-hydroxyvitamin D