DNA 修复基因变异与结直肠癌的关联：风险、毒性和生存。
Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival.
机构信息
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Östra, 416 85, Gothenburg, Sweden.
Digestive Oncology Research Centre, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
BMC Cancer. 2020 May 12;20(1):409. doi: 10.1186/s12885-020-06924-z.
BACKGROUND
Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy.
METHODS
SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan-Meier method and log-rank test was used to measure the effects of the SNPs on RFS and OS.
RESULTS
The CC genotype of ERCC2-rs238406 and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy (p = 0.03). Also, more patients with the ERCC2-rs13181 C allele needed dose reduction compared to patients with the A/A genotype (p = 0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared to those with the T/T genotype (p = 0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype (p = 0.006 and p = 0.004, respectively). ERCC2- rs238406 C/C was also associated with a higher frequency of thrombocytopenia (p = 0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele (p = 0.02). However, there was no significant association between the SNPs and 5-year RFS.
CONCLUSIONS
Both SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC.
背景
DNA 修复基因中的单核苷酸多态性（SNP）在预测治疗结果方面具有潜在的临床价值。在本研究中，我们研究了 XRCC1-rs25487、ERCC1-rs11615、ERCC2-rs238406 和 ERCC2-rs13181 基因中的 SNP 与结直肠癌（CRC）风险、无复发生存（RFS）、总生存（OS）以及化疗期间毒性之间的关系。
方法
采用 TaqMan 技术对 590 例 CRC 病例和 300 例对照进行 SNP 分析。采用卡方检验分析 SNP 与 CRC 风险和化疗期间毒性的关系。采用 Kaplan-Meier 方法和对数秩检验测量 SNP 对 RFS 和 OS 的影响。
结果
ERCC2-rs238406 的 CC 基因型和 ERCC2-rs13181 的 C 等位基因与 CRC 风险显著增加相关。ERCC1-rs11615 基因型 TT 与辅助化疗中的口腔炎有关（p=0.03）。此外，与 ERCC2-rs13181 的 A/A 基因型相比，携带该基因的 C 等位基因的患者需要减少剂量（p=0.02）。在一线化疗中，与 ERCC1-rs11615 的 T/T 基因型相比，携带该基因的 C 等位基因的患者更容易出现恶心（p=0.04），与 ERCC2-rs13181 的 A/A 基因型相比，该基因的 C 等位基因更容易出现眼反应和血小板减少症（p=0.006 和 p=0.004）。与 ERCC2-rs238406 的 A/A 基因型相比，携带该基因的 C/C 基因型也与血小板减少症的发生率更高相关（p=0.03）。I 期和 II 期 CRC 患者携带 ERCC2-rs238406 的 C 等位基因时，5 年 OS 更短（p=0.02）。然而，SNP 与 5 年 RFS 之间没有显著相关性。
结论
ERCC2 中的两个 SNP 都与 CRC 风险以及一线治疗期间的毒性有关。此外，ERCC2-rs238406 与早期 CRC 的 OS 相关。ERCC1-rs11615 变体与辅助化疗期间的毒性有关。结果支持之前的发现，即 ERCC1 和 ERCC2 中的 SNP 在 CRC 的临床管理中具有预后和预测价值。
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