Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients.
Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients.
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lncRNA-p53调控网络基因的遗传多态性与鼻咽癌患者同步放化疗的毒性和疗效相关
DOI：
10.1038/s41598-017-08890-2
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发表时间：
2017-08-16
影响因子：
4.6
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Wang Y;Guo Z;Zhao Y;Jin Y;An L;Wu B;Liu Z;Chen X;Chen X;Zhou H;Wang H;Zhang W
转录因子p53在癌症中的相关性是不可否认的，并且许多lncRNA作为调节剂或效应物参与p53调节网络，以p53依赖性方式触发导致DNA损伤后细胞停滞或凋亡的转录应答。尽管NPC的治疗反应有所改善，但人们对不良反应的易感性和治疗效果仍然存在异质性。因此，我们分析了505例NPC患者发现队列中lncRNA-p53调控网络中5个基因的8个潜在功能SNP。通过进行多变量逻辑回归，研究了遗传变异对CRT诱导毒性的疗效和风险的影响。最引人注目的发现是MEG 3rs 10132552 CC基因型使3-4级贫血的发生风险增加3倍以上（OR = 3.001，95%CI = 1.355- 6.646，P = 0.007）。rs 10132552 CT基因型对治疗反应较好（OR = 0.261，95%CI = 0.089- 0.770，P = 0.015）。携带LINC-RORrs 2027701并伴有一个或两个变异等位基因的个体与降低的心绞痛风险有显著相关性（OR = 0.503，95%CI = 0.303- 0.835，P = 0.008）。总之，我们的研究结果表明，lncRNA-p53调控网络的遗传多态性可能在降低治疗相关毒性和改善NPC患者的预后方面发挥潜在作用。
The relevance of the transcription factor p53 in cancer is inarguable, and numerous lncRNAs are involved in the p53 regulatory network as either regulators or effectors, triggering a transcriptional response that causes either cell arrest or apoptosis following DNA damage in a p53-dependent manner. Despite the fact that the therapeutic response is improved in NPC, heterogeneity among people remains with regard to the susceptibility of adverse effects and the efficacy of treatments. Therefore, we analysed eight potentially functional SNPs of five genes in the lncRNA-p53 regulatory network in a discovery cohort of 505 NPC patients. By performing multivariate logistic regression, the impact of genetic variations on the efficacy and risk of CRT-induced toxicities was investigated. The most dramatic finding was that theMEG3rs10132552 CC genotype had a greater than three-fold increased risk of developing grade 3–4 anaemia (OR = 3.001, 95%CI = 1.355–6.646,P= 0.007). Furthermore, the rs10132552 CT genotype had a better response to treatment (OR = 0.261, 95%CI = 0.089–0.770,P= 0.015). Individuals carryingLINC-RORrs2027701 with one or two variant alleles had significant associations with a reduced risk of neutropaenia (OR = 0.503, 95%CI = 0.303–0.835,P= 0.008). In conclusion, our results suggested that genetic polymorphisms of the lncRNA-p53 regulatory network could play a potential role in reducing treatment-related toxicities and improving outcomes for NPC patients.
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影响因子：
16.6
作者：
Sanchez, Yolanda;Segura, Victor;Marin-Bejar, Oskar;Athie, Alejandro;Marchese, Francesco P.;Gonzalez, Jovanna;Bujanda, Luis;Guo, Shuling;Matheu, Ander;Huarte, Maite
通讯作者：
Huarte, Maite
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
--
作者：
Jia M;Zhu M;Wang M;Sun M;Qian J;Ding F;Chang J;Wei Q
通讯作者：
Wei Q
DOI：
10.1002/hed.20833
发表时间：
2008-07
影响因子：
2.9
作者：
Chou, Josephine;Lin, Yu-Ching;Kim, Jae;You, Liang;Xu, Zhidong;He, Biao;Jablons, David M.
通讯作者：
Jablons, David M.
影响因子：
7.4
作者：
Qi P;Xu MD;Ni SJ;Huang D;Wei P;Tan C;Zhou XY;Du X
通讯作者：
Du X