| Title: | Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation |
| Journal: | British Journal of Cancer |
| Published: | 13 Mar 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38480934/ |
| DOI: | https://doi.org/10.1038/s41416-024-02643-5 |
| URL: | https://www.nature.com/articles/s41416-024-02643-5.pdf |
Publication 10125
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Abstract
BackgroundTo investigate the association between circulating 25-hydroxyvitamin D (25-OHD) and colorectal cancer (CRC) survival outcomes.MethodsWe 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.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.</p>
13 Authors
- Xiaomeng Zhang
- Yazhou He
- Xue Li
- Rasha Shraim
- Wei Xu
- Lijuan Wang
- Susan M. Farrington
- Harry Campbell
- Maria Timofeeva
- Lina Zgaga
- Peter Vaughan-Shaw
- Evropi Theodoratou
- Malcolm G. Dunlop
1 Application
| Application ID | Title |
|---|---|
| 7441 | Investigation of genetic, environment and gene ? environment interaction in colorectal cancer risk and survival |
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