The impacts of genetic polymorphisms in genes of base excision repair pathway on the efficacy and acute toxicities of (chemo)radiotherapy in patients with nasopharyngeal carcinoma.
The impacts of genetic polymorphisms in genes of base excision repair pathway on the efficacy and acute toxicities of (chemo)radiotherapy in patients with nasopharyngeal carcinoma.
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DOI：
10.18632/oncotarget.20203
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发表时间：
2017-10-03
期刊：
影响因子：
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通讯作者：
Li J
中科院分区：
文献类型：
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作者：
Wang J;Guo C;Gong X;Ao F;Huang Y;Huang L;Tang Y;Jiang C;Xie X;Dong Q;Huang M;Li J
探讨碱基切除修复（BER）通路基因多态性是否是鼻咽癌（NPC）患者放化疗预后的预测因子。我们对174例接受（化疗）放疗的鼻咽癌患者BER通路中3个基因的5个潜在功能性单核苷酸多态性（SNP）进行了基因分型。Sequenom MassArray用于SNP分析。采用实体瘤疗效评价标准（RECIST）评价放疗结束时和放疗后3个月的疗效。采用放射治疗肿瘤学组和欧洲癌症研究和治疗组织（RTOG/EORTC）急性放射发病率评分标准对急性放射毒性进行评分。多因素分析采用Logistic回归分析。我们发现X射线修复交叉互补基因1（XRCC 1）rs 25489的宽基因型GG（GG vs GA：OR=3.833，95%CI=1.512-9.714，P=0.005; GG vs GA+AA：OR=3.610，95%CI=1.496-8.713，P=0.004）和8-氧代鸟嘌呤DNA糖基化酶（OGG 1）rs 1052133的宽基因型CC CC与GG：OR=0.263，95%CI=0.073-0.951，P=0.042; CC与CG+GG：OR=0.454，95%CI=0.195-1.053，P=0.066）分别与放疗结束时的原发肿瘤疗效呈正相关和负相关。与此相反，BER基因多态性与治疗后3个月的治疗结果或治疗相关的急性毒性之间没有关联。BER基因的SNPs可能作为（化疗）放疗疗效的生物标志物。准确评价尚需进一步的长期随访和大样本研究。
To explore whether polymorphisms in base excision repair (BER) pathway genes are predictors of (chemo)radiotherapy outcome in patients with nasopharyngeal carcinoma (NPC). We genotyped five potentially functional single nucleotide polymorphisms (SNPs) of three genes in the BER pathway in 174 NPC patients who were treated with (chemo)radiotherapy. Sequenom MassArray was used for SNPs analysis. The efficacy at the end of radiotherapy and at 3 months after radiotherapy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Acute radiation toxicity was scored using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) acute radiation morbidity scoring criteria. Logistic regression was employed to assess the multivariate analyses. We found that the wide genotype GG of X-ray repair cross-complementing 1 (XRCC1) rs25489 (GG vs GA: OR=3.833, 95%CI=1.512-9.714, P=0.005; GG vs GA+AA: OR=3.610, 95%CI=1.496-8.713, P=0.004) and the wide genotype CC of 8-oxoguanine DNA glycosylase (OGG1) rs1052133 (CC vs GG: OR=0.263, 95%CI=0.073-0.951, P=0.042; CC vs CG+GG: OR=0.454, 95%CI=0.195-1.053, P=0.066) were positively and negatively associated with primary tumor efficacy at the end of radiotherapy, respectively. By contrast, no association was found between BER gene polymorphisms and the treatment outcomes at 3 months post-treatment or the treatment-related acute toxicities. The SNPs of the BER genes may act as biomarkers for the curative effect of (chemo)radiotherapy. Further study with long-time follow-up and large population is needed for accurate assessment.