miRNA 种子区遗传变异与直肠癌患者术后放化疗后急性不良事件及生存的关系。
Associations of Genetic Variations in MicroRNA Seed Regions With Acute Adverse Events and Survival in Patients With Rectal Cancer Receiving Postoperative Chemoradiation Therapy.
机构信息
State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Etiology & Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):1026-1033. doi: 10.1016/j.ijrobp.2017.12.256. Epub 2017 Dec 21.
PURPOSE
The aim of this study was to investigate the associations between single nucleotide polymorphisms (SNPs) in the seed regions of microRNAs and acute adverse events (AEs) and survival in patients with rectal cancer receiving postoperative chemoradiation therapy.
METHODS AND MATERIALS
Eighteen SNPs were genotyped in 365 patients with rectal cancer receiving postoperative chemoradiation therapy. The associations between genotypes and AEs were estimated by odds ratios and 95% confidence intervals (CIs), which were computed by using multivariate logistic regression models. The hazard ratios and 95% CIs to assess the death of patients for different genotypes were calculated by Cox proportional regression models. Overall survival and disease-free survival of patients with different genotypes were estimated by Kaplan-Meier plots, and the statistical significance was determined by using the log-rank test.
RESULTS
In these patients, the most common grade ≥2 AEs were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). With false discovery rate correction, SNP rs2273626 was significantly associated with a decreased risk of grade ≥2 leukopenia (odds ratio, 0.48; 95% CI, 0.31-0.74; P = .0009). In addition, SNP rs202195689 was associated with overall survival and disease-free survival in patients receiving postoperative chemoradiation therapy, with the hazard ratios for death being 2.02 (95% CI, 1.36-3.01; P = .0006) and 1.91 (95% CI, 1.36-2.70; P = .0002), respectively. However, no significant association between these SNPs and diarrhea and dermatitis was observed.
CONCLUSIONS
These results suggest that rs2273626 and rs202195689 in microRNA seed regions might serve as independent biomarkers for predicting AEs and prognosis in patients with rectal cancer receiving postoperative chemoradiation therapy. Independent replication of these findings is required to confirm these results.
目的
本研究旨在探讨微小 RNA 种子区单核苷酸多态性（SNPs）与直肠癌患者接受术后放化疗后急性不良事件（AEs）和生存的相关性。
方法与材料
对 365 例接受术后放化疗的直肠癌患者进行了 18 个 SNP 的基因分型。通过多变量逻辑回归模型计算比值比和 95%置信区间（CI），以估计基因型与 AEs 之间的相关性。通过 Cox 比例风险回归模型计算不同基因型患者死亡的风险比和 95%CI。通过 Kaplan-Meier 图评估不同基因型患者的总生存率和无病生存率，采用对数秩检验确定统计学意义。
结果
在这些患者中，最常见的≥2 级 AEs 为腹泻（44.1%）、白细胞减少（29.6%）和皮炎（18.9%）。经假发现率校正后，SNP rs2273626 与≥2 级白细胞减少症的风险降低显著相关（比值比，0.48；95%CI，0.31-0.74；P =.0009）。此外，SNP rs202195689 与接受术后放化疗的患者的总生存率和无病生存率相关，死亡的风险比分别为 2.02（95%CI，1.36-3.01；P =.0006）和 1.91（95%CI，1.36-2.70；P =.0002）。然而，这些 SNP 与腹泻和皮炎之间没有显著相关性。
结论
这些结果表明，微小 RNA 种子区的 rs2273626 和 rs202195689 可能作为预测直肠癌患者接受术后放化疗后 AEs 和预后的独立生物标志物。需要对这些发现进行独立复制以确认这些结果。
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