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Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy

查看全文 作　　者：Hongxia [1]Chen;Luxi [1]Yin;Jie [1]Yang;Ningxin [1]Ren;Jinna [1]Chen;Qixuan [1]Lu;Ying [1]Huang;Yanru [2]Feng;Weihu [2]Wang;Shulian [2]Wang;Yueping [2]Liu;Yongwen [2]Song;Yexiong [2]Li;Jing [2]Jin;Wen [1]Tan;Dongxin [1,3]Lin 高影响力作者 机构地区：[1]State Key Laboratory of Molecular Oncology,Department of Etiology and Carcinogenesis,Beijing Key Laboratory for Carcinogenesis and Cancer Prevention,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;[2]Department of Radiation Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;[3]Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Guangzhou 510060,China高影响力机构 出　　处：《Cancer Biology & Medicine》索引2023年第20卷第4期,共20页高影响力期刊 基　　金：supported by grants from the National Natural Science Foundation(Grant No.81972859 to WT);CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2019-I2M-1-003 to WT);the State Key Laboratory of Molecular Oncology Grant(Grant No.SKLMO-2021-03 to WT). 摘　　要：Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment. 关 键 词：Rectal neoplasms genetic variation regulated cell death overall survival ALOX5
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