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.

中文翻译：

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循环 25-羟基维生素 D 与结直肠癌的生存结果：来自基于人群的前瞻性队列和孟德尔随机化的证据

背景

旨在研究循环 25-羟基维生素 D (25-OHD) 与结直肠癌 (CRC) 生存结果之间的关联。

方法

我们在苏格兰结直肠癌研究 (SOCCS) 和英国生物银行 (UKBB) 之间进行了分析。检查了癌症特异性生存（CSS）和总生存（OS）结果。25-OHD 水平分为三组，并应用多变量 Cox 比例风险模型来估计风险比 (HR)。我们通过生成的 25-OHD 多基因风险评分 (PRS) 进行个体水平孟德尔随机化 (MR)，并使用逆方差加权 (IVW) 方法进行汇总水平 MR。

结果

我们观察到 CSS (HR = 0.65,95%CI = 0.55–0.76, P  = 1.03 × 10 ⁻⁷ ) 和 OS (HR = 0.66,95%CI = 0.58–0.75, P  = 8.15 × 10 ⁻¹¹ )明显较差调整协变量后，与 25-OHD 最高的患者相比，具有最低 25-OHD 的患者。这些关联在不同肿瘤部位和阶段的患者中仍然存在。然而，我们发现 25-OHD PRS 与 CSS（HR = 0.98，95%CI = 0.80–1.19，P  = 0.83）或 OS（HR = 1.07，95%CI = 0.91–1.25，P  = 0.42 ）之间没有显着关联。 ）。此外，通过对 CSS (IVW:HR = 1.04,95%CI = 0.85–1.28, P  = 0.70) 或 OS (IVW:HR = 1.10,95%CI = 1.10,95%CI)进行汇总级 MR 分析，我们没有发现因果效应的证据。= 0.93–1.31，P  = 0.25）。

结论

这项研究支持观察到的循环 25-OHD 较低与 CRC 患者较差的生存结果之间的关联。虽然更好的结果和更高的 25-OHD 之间的基因型特异性关联很有趣，但我们没有发现使用 MR 方法支持因果关系。