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Background <p>Circulating 25-hydroxyvitamin D [25(OH)D] levels and genetic polymorphisms in the vitamin D receptor (VDR) have been explored as potential prognostic factors in colorectal cancer (CRC). This study aimed to investigate the association between circulating 25(OH)D levels and CRC prognostic outcomes, with a narrative evaluation of VDR polymorphisms.</p> Methods <p>We performed a systematic literature search in the Cochrane Library, PubMed, ScienceDirect, and Scopus. The primary outcomes were CRC-specific survival, overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using the random-effects model with inverse variance weighting, comparing high versus low 25(OH)D levels. Due to heterogeneity in genetic models and limited available data, VDR polymorphisms were synthesized using a narrative approach.</p> Results <p>Of the 61 studies included in the systematic review, 35 studies were included in the meta-analysis, which showed that higher 25(OH)D levels were associated with a lower risk of mortality, including a 26% lower CRC-specific mortality (HR 0.74; 95% CI 0.69–0.80; I<sup>2</sup> = 0.01%), a 32% lower overall mortality (HR 0.68; 95% CI 0.64–0.72; I<sup>2</sup> = 7.6%), and improved DFS (HR 0.71; 95% CI 0.61–0.83; I<sup>2</sup> = 36.8%). The prognostic roles of VDR polymorphisms, particularly rs7975232 (<i>ApaI</i>), rs1544410 (<i>BsmI</i>), rs2228570 / rs10735810 (<i>FokI</i>), and rs731236 (<i>TaqI</i>) with CRC outcomes, including CRC-specific survival, OS, and DFS were reported across 18 studies.</p> Conclusion <p>This study provides quantitative evidence supporting the potential prognostic relevance of circulating vitamin D levels in CRC. The role of VDR genetic polymorphisms remains inconclusive, warranting further investigations.</p> Trial registration <p>The protocol of this systematic review and meta-analysis has been registered on PROSPERO (<a href="https://www.crd.york.ac.uk/PROSPERO/">https://www.crd.york.ac.uk/PROSPERO/</a>), with the registration number CRD42024575841.</p>

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Circulating vitamin D status and prognosis in colorectal cancer: a systematic review and meta-analysis with exploratory evidence on vitamin D receptor polymorphisms

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月16日

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  • Daylia Thet,
  • Nutthada Areepium,
  • Chidchanok Rungruang,
  • Nattawut Leelakanok,
  • Tippawan Siritientong

摘要

Background

Circulating 25-hydroxyvitamin D [25(OH)D] levels and genetic polymorphisms in the vitamin D receptor (VDR) have been explored as potential prognostic factors in colorectal cancer (CRC). This study aimed to investigate the association between circulating 25(OH)D levels and CRC prognostic outcomes, with a narrative evaluation of VDR polymorphisms.

Methods

We performed a systematic literature search in the Cochrane Library, PubMed, ScienceDirect, and Scopus. The primary outcomes were CRC-specific survival, overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using the random-effects model with inverse variance weighting, comparing high versus low 25(OH)D levels. Due to heterogeneity in genetic models and limited available data, VDR polymorphisms were synthesized using a narrative approach.

Results

Of the 61 studies included in the systematic review, 35 studies were included in the meta-analysis, which showed that higher 25(OH)D levels were associated with a lower risk of mortality, including a 26% lower CRC-specific mortality (HR 0.74; 95% CI 0.69–0.80; I2 = 0.01%), a 32% lower overall mortality (HR 0.68; 95% CI 0.64–0.72; I2 = 7.6%), and improved DFS (HR 0.71; 95% CI 0.61–0.83; I2 = 36.8%). The prognostic roles of VDR polymorphisms, particularly rs7975232 (ApaI), rs1544410 (BsmI), rs2228570 / rs10735810 (FokI), and rs731236 (TaqI) with CRC outcomes, including CRC-specific survival, OS, and DFS were reported across 18 studies.

Conclusion

This study provides quantitative evidence supporting the potential prognostic relevance of circulating vitamin D levels in CRC. The role of VDR genetic polymorphisms remains inconclusive, warranting further investigations.

Trial registration

The protocol of this systematic review and meta-analysis has been registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), with the registration number CRD42024575841.