最近的随机临床试验的荟萃分析发现，每日补充维生素D3对癌症死亡有积极影响，尽管结果仍然有争议。为了调查维生素D补充是否减少对p53免疫反应的消化道癌症患者的复发或死亡风险，本文通过后期亚组分析AMATERASU随机、双盲、安慰剂对照临床试验的数据。该试验于2019年报道，包括2010年1月至2018年2月期间在日本一所大学医院收治的消化道癌症患者，随访中位数（IQR）为3.5（2.5-5.3）年，以比较维生素D补充和安慰剂的效果。纳入了AMATERASU试验中的417名患者中残余血清样本可获取的患者。数据分析于2022年10月20日至11月24日期间进行。 维生素D3（每天2000 IU）补充或安慰剂。 主要结果是5年的复发或死亡。p53免疫反应亚组的患者通过血清中抗p53抗体的阳性和在癌细胞中p53抑癌蛋白的核积累超过99%来定义，这被认为是p53错义突变的生物标志物。抗p53抗体水平通过化学发光酶免疫分析测定。病理标本中癌组织中p53蛋白的免疫组化染色数据来自先前的研究，并分为4个等级。 在392例消化道癌患者中（平均[SD]年龄66 [10.7]岁；男性260名[66.3%]），有37例食管癌（9.4%），170例胃癌（43.4%），2例小肠癌（0.5%）和183例结直肠癌（46.7%）。142名患者（36.2%）可检测到抗p53抗体，p53-免疫组织化学染色等级与血清抗p53抗体水平呈正相关（系数=0.19；P<.001）。在p53免疫反应亚组（80名患者）中，维生素D组中有9名患者（16.7%）发生复发或死亡，安慰剂组中有14名患者（53.8%）；5年无复发生存率（RFS）在维生素D组（13名患者[80.9%]）显著高于安慰剂组（1名患者[30.6%]；风险比[HR]0.27，95% CI0.11-0.61；P=.002）。这与非p53免疫反应亚组中的272名患者显著不同，其中维生素D对5年RFS无影响（维生素D：158例患者中的35例[22.2%] vs 安慰剂：114例患者中的24例[21.1%]；HR1.09，95% CI0.65-1.84）（相互作用的P=.005）。 该研究发现，维生素D补充减少了消化道癌症患者p53免疫反应亚组的复发或死亡风险。 识别号：UMIN000001977。

Recent meta-analyses of randomized clinical trials found that daily vitamin D3 supplementation had beneficial effects on cancer mortality, although the results are still controversial.To examine whether vitamin D supplementation reduces the risk of relapse or death in a supgroup of patients with digestive tract cancer who were p53 immunoreactive.This was a post hoc subgroup analysis of the AMATERASU randomized, double-blind, placebo-controlled clinical trial. This trial included patients at a single university hospital in Japan with digestive tract cancers between January 2010 and February 2018 followed up for a median (IQR) of 3.5 (2.5-5.3) years to compare the effects of vitamin D supplementation with placebo and was reported in 2019. Patients from among 417 participants in the AMATERASU trial whose residual serum samples were available were included. Data were analyzed from October 20 to November 24, 2022.Vitamin D3 (2000 IU/d) supplementation or placebo.The primary outcome was 5-year relapse or death. The subgroup of patients who were p53 immunoreactive was defined by positivity for anti-p53 antibodies in serum and nuclear accumulation of p53 oncosuppressor protein in more than 99% of cancer cells, which is considered a biomarker for p53 missense mutations. Anti-p53 antibody levels were measured using chemiluminescent enzyme immune assay. Immunohistochemical staining data of p53 protein in cancer tissue in pathologic specimens were obtained from a previous study and divided into 4 grades.Among 392 patients with digestive tract cancer (mean [SD] age, 66 [10.7] years; 260 males [66.3%]), there were 37 patients with esophageal cancer (9.4%), 170 patients with gastric cancer (43.4%), 2 patients with small bowel cancer (0.5%), and 183 patients with colorectal cancer (46.7%). Serum anti-p53 antibody was detectable in 142 patients (36.2%), and p53-immunohistochemistry grade showed a positive association with serum anti-p53 antibody levels (coefficient = 0.19; P < .001). In the p53-immunoreactive subgroup (80 patients), relapse or death occurred in 9 of 54 patients (16.7%) in the vitamin D group and 14 of 26 patients (53.8%) in the placebo group; 5-year relapse-free survival (RFS) was significantly higher in the vitamin D group (13 patients [80.9%]) than the placebo group (1 patient [30.6%]; hazard ratio [HR], 0.27; 95% CI, 0.11-0.61; P = .002). This was significantly different from 272 patients in the non-p53 immunoreactive subgroup, in which vitamin D had no effect on 5-year RFS (vitamin D: 35 of 158 patients [22.2%] vs placebo: 24 of 114 patients [21.1%]; HR, 1.09; 95% CI, 0.65-1.84) (P for interaction = .005).This study found that vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients with digestive tract cancer who were p53 immunoreactive.Identifier: UMIN000001977.