Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Cancer Epidemiol Biomarkers Prev. 2020 Nov;29(11):2323-2331. doi: 10.1158/1055-9965.EPI-20-0291. Epub 2020 Sep 11.
Higher total 25-hydroxyvitamin D [25(OH)D] levels are associated with improved survival among patients with colorectal cancer, but the relationships between circulating vitamin D binding protein (VDBP), and bioavailable or free 25(OH)D, and colorectal cancer survival remain unknown.
We examined the associations between prediagnostic plasma levels of vitamin D-related markers and survival among 603 White participants diagnosed with colorectal cancer from two prospective U.S. cohorts. Plasma VDBP and total 25(OH)D were directly measured, while bioavailable and free 25(OH)D was calculated using a validated formula on the basis of total 25(OH)D, VDBP, and albumin levels. Cox proportional hazards regression was used to estimate HRs for overall and colorectal cancer-specific mortality, with adjustment for other prognostic markers and potential confounders.
Higher VDBP levels were associated with improved overall ( = 0.001) and colorectal cancer-specific survival ( = 0.02). Compared with patients in the lowest quartile, those in the highest quartile of VDBP had a multivariate HR of 0.58 [95% confidence interval (CI), 0.41-0.80] for overall mortality and 0.58 (95% CI, 0.37-0.91) for colorectal cancer-specific mortality. The results remained similar after further adjustment for total 25(OH)D levels. In contrast, neither bioavailable nor free 25(OH)D levels were associated with overall or colorectal cancer-specific mortality (all > 0.15).
Prediagnostic circulating concentrations of VDBP were positively associated with survival among patients with colorectal cancer.
The clinical utility of VDBP as a prognostic marker warrants further exploration, as well as research into underlying mechanisms of action.
更高的总 25-羟维生素 D [25(OH)D]水平与结直肠癌患者的生存改善相关,但循环维生素 D 结合蛋白 (VDBP)与生物可利用或游离 25(OH)D 之间的关系以及结直肠癌的生存关系尚不清楚。
我们研究了维生素 D 相关标志物的预测血浆水平与来自两个美国前瞻性队列的 603 名白人结直肠癌患者生存之间的关系。直接测量血浆 VDBP 和总 25(OH)D,而生物可利用和游离 25(OH)D 则根据总 25(OH)D、VDBP 和白蛋白水平使用经过验证的公式计算。使用 Cox 比例风险回归来估计总死亡率和结直肠癌特异性死亡率的 HR,同时调整其他预后标志物和潜在混杂因素。
更高的 VDBP 水平与整体( = 0.001)和结直肠癌特异性生存( = 0.02)改善相关。与最低四分位数的患者相比,VDBP 最高四分位数的患者总死亡率的多变量 HR 为 0.58(95%CI,0.41-0.80),结直肠癌特异性死亡率为 0.58(95%CI,0.37-0.91)。进一步调整总 25(OH)D 水平后,结果仍然相似。相比之下,生物可利用或游离 25(OH)D 水平均与总死亡率或结直肠癌特异性死亡率无关(均 > 0.15)。
预测血浆中 VDBP 的循环浓度与结直肠癌患者的生存呈正相关。
VDBP 作为预后标志物的临床应用价值值得进一步探讨,同时也需要研究其作用机制。