Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
Cancer Epidemiol Biomarkers Prev. 2020 Jun;29(6):1128-1134. doi: 10.1158/1055-9965.EPI-19-1409. Epub 2020 Mar 18.
Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in patients with colorectal cancer have been consistently associated with higher mortality in observational studies. It is unclear whether low 25(OH)D levels directly influence colorectal cancer mortality. To minimize bias, we use genetic variants associated with vitamin D levels to evaluate the association with overall and colorectal cancer-specific survival.
Six genetic variants have been robustly identified to be associated with 25(OH)D levels in genome-wide association studies. On the basis of data from the International Survival Analysis in Colorectal Cancer Consortium, the individual genetic variants and a weighted genetic risk score were tested for association with overall and colorectal cancer-specific survival using Cox proportional hazards models in 7,657 patients with stage I to IV colorectal cancer, of whom 2,438 died from any cause and 1,648 died from colorectal cancer.
The 25(OH)D decreasing allele of SNP rs2282679 ( gene, encodes group-specific component/vitamin D-binding protein) was associated with poorer colorectal cancer-specific survival, although not significant after multiple-testing correction. None of the other five SNPs showed an association. The genetic risk score showed nonsignificant associations with increased overall [HR = 1.54; confidence interval (CI), 0.86-2.78] and colorectal cancer-specific mortality (HR = 1.76; 95% CI, 0.86-3.58). A significant increased risk of overall mortality was observed in women (HR = 3.26; 95% CI, 1.45-7.33; = 0.01) and normal-weight individuals (HR = 4.14; 95% CI, 1.50-11.43, = 0.02).
Our results provided little evidence for an association of genetic predisposition of lower vitamin D levels with increased overall or colorectal cancer-specific survival, although power might have been an issue.
Further studies are warranted to investigate the association in specific subgroups.
在观察性研究中，患有结直肠癌的患者血清 25-羟维生素 D [25(OH)D]浓度较低与死亡率较高一直相关。目前尚不清楚低 25(OH)D 水平是否直接影响结直肠癌的死亡率。为了最大程度地减少偏倚，我们使用与维生素 D 水平相关的遗传变异来评估其与总生存期和结直肠癌特异性生存期的关系。
在全基因组关联研究中，已经确定了六个与 25(OH)D 水平密切相关的遗传变异。基于国际结直肠癌生存分析联盟的数据，在 7657 例 I 至 IV 期结直肠癌患者中，使用 Cox 比例风险模型，通过个体遗传变异和加权遗传风险评分，测试其与总生存期和结直肠癌特异性生存期的相关性，其中 2438 例患者死于任何原因，1648 例患者死于结直肠癌。
SNP rs2282679（基因，编码组特异性成分/维生素 D 结合蛋白）的 25(OH)D 降低等位基因与结直肠癌特异性生存率较差相关，但在多次检验校正后无统计学意义。其他五个 SNP 均无关联。遗传风险评分与总生存期（HR=1.54；95%CI，0.86-2.78）和结直肠癌特异性死亡率（HR=1.76；95%CI，0.86-3.58）增加均无显著相关性。在女性（HR=3.26；95%CI，1.45-7.33；P=0.01）和正常体重个体（HR=4.14；95%CI，1.50-11.43，P=0.02）中观察到总死亡率的风险显著增加。
我们的研究结果提供的证据表明，较低的维生素 D 水平的遗传易感性与总生存期或结直肠癌特异性生存期的增加无关，尽管可能存在效力问题。
需要进一步的研究来调查特定亚组的相关性。
