Stojkovic Lalosevic Milica, Coric Vesna, Pekmezovic Tatjana, Simic Tatjana, Pavlovic Markovic Aleksandra, Pljesa Ercegovac Marija
Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 11000 Belgrade, Serbia.
Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Medicina (Kaunas). 2024 Mar 28;60(4):553. doi: 10.3390/medicina60040553.
: Despite improvements in screening programs, a large number of patients with colorectal cancer (CRC) are diagnosed in an advanced disease stage. Previous investigations imply that glutathione transferases (GSTs) might be associated with the development and progression of CRC. Moreover, the detoxification mechanism of oxaliplatin, which represents the first line of treatment for advanced CRC, is mediated via certain GSTs. The aim of this study was to evaluate the significance of certain genetic variants on CRC prognosis and the efficacy of oxaliplatin-based treatment. : This prospective study included 523 patients diagnosed with CRC in the period between 2014 and 2016, at the Digestive Surgery Clinic, University Clinical Center of Serbia, Belgrade. Patients were followed for a median of 43.47 ± 17.01 months (minimum 1-63 months). Additionally, 109 patients with advanced disease, after surgical treatment, received FOLFOX6 treatment as a first-line therapy between 2014 and 2020. The - method was used to analyze cumulative survival, and the Cox proportional hazard regression model was used to study the effects of different genotypes on overall survival. : Individuals with the genotype and the ( genotype had significantly shorter survival when compared to referent genotypes ( and ) (log-rank: = 0.001). Moreover, individuals with the genotype who received 5-FU-based treatment had statistically significantly shorter survival when compared to individuals with the (log-rank: = 0.05). : Both GSTM1-null and GSTP1 IleVal+ValVal () genotypes are associated with significantly shorter survival in CRC patients. What is more, the genotype is associated with shorter survival in patients receiving FOLOFOX6 treatment.
尽管筛查项目有所改进，但仍有大量结直肠癌（CRC）患者在疾病晚期被诊断出来。先前的研究表明，谷胱甘肽转移酶（GSTs）可能与CRC的发生和发展有关。此外，作为晚期CRC一线治疗药物的奥沙利铂的解毒机制是通过某些GSTs介导的。本研究的目的是评估某些基因变异对CRC预后的意义以及基于奥沙利铂治疗的疗效。：这项前瞻性研究纳入了2014年至2016年期间在贝尔格莱德塞尔维亚大学临床中心消化外科诊所诊断为CRC的523例患者。患者的中位随访时间为43.47±17.01个月（最短1 - 63个月）。此外，109例晚期疾病患者在手术治疗后，于2014年至2020年期间接受FOLFOX6治疗作为一线治疗。采用该方法分析累积生存率，并使用Cox比例风险回归模型研究不同基因型对总生存的影响。：与参照基因型（和）相比，基因型和（基因型的个体生存时间明显缩短（对数秩检验：= 0.001）。此外，接受基于5 - FU治疗的基因型个体与（基因型个体相比，生存时间在统计学上显著缩短（对数秩检验：= 0.05）。：GSTM1缺失和GSTP1 IleVal + ValVal（）基因型均与CRC患者的生存时间显著缩短有关。此外，基因型与接受FOLFOX6治疗的患者生存时间缩短有关。
