GSTP1 Ile105Val and GPX1 Pro198Leu Polymorphisms and Their Association with Response to Radiotherapy in Nasopharyngeal Carcinoma Patients

Raja Benzeid
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Abstract

Objectives: Radio-resistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment. Due to individual variations in radio-sensitivity, biomarkers are needed to tailor radiation treatment. Within this frame, the identification of series of genetic signatures mainly SNPs for NPC patients treated with radiotherapy may help to predict treatment outcome and deliver personalized therapy. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val and GPX1 Pro198Leu polymorphisms and response to radiotherapy in NPC patients. Methods: From September 2016 to October 2018, a total of 101 patients with confirmed NPC, recruited at Mohammed IV Center for Treatment of Cancer of Casablanca, underwent radiotherapy. DNA was extracted from peripheral blood. Genotyping of the GPX1 Pro198Leu and GPX1 Val105Leu polymorphisms was carried out by PCR amplification and DNA sequencing. SPSS was used to analyse the association of GSTP1 and GPX1 genotypes with clinico-pathological features and response to radiotherapy. Results: The genotyping data revealed the presence of only two genotypes namely Pro/Pro (57.4%) and Pro/Leu (40.6%) for GPX1 gene. The allelic frequencies of C and T alleles were 78.7% and 21.3% respectively. For GSTP gene, the homozygous genotypes Val/Val and Leu/Leu were detected in 35.6% and 12.9% of patients respectively. The heterozygous genotype Val/Leu prevailed (51.5%). Allelic frequencies showed the presence of the two alleles A and G in 57.1% and 42.9% patients respectively. Statistical analysis failed to find any significant association between GSTP Val105Ile and GPX1 Pro198Leu genetic polymorphisms and socio-demographic and clinico-pathological features as well as response to radiotherapy (p>0.05). Conclusion: Further research is warranted on the potential role of SNPs within antioxidant defines genes in radiotherapy response and to identify reliable predictive and non-invasive biomarkers for radio-resistance among NPC patients for personalised therapies. Abstract Polymorphisms and Their Association with Response to Radiotherapy in Carcinoma
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鼻咽癌患者GSTP1 Ile105Val和GPX1 Pro198Leu多态性及其与放疗应答的关系
目的:放射耐药是鼻咽癌治疗的主要挑战。由于放射敏感性的个体差异,需要生物标志物来定制放射治疗。在这一框架内,识别一系列主要是snp的鼻咽癌放疗患者的遗传特征可能有助于预测治疗结果并提供个性化治疗。本研究的目的是评估GSTP1 Ile105Val和GPX1 Pro198Leu多态性与鼻咽癌患者放疗反应之间的可能关联。方法:2016年9月至2018年10月,在卡萨布兰卡穆罕默德四世癌症治疗中心招募101例确诊的鼻咽癌患者进行放疗。从外周血提取DNA。通过PCR扩增和DNA测序对GPX1 Pro198Leu和GPX1 Val105Leu多态性进行基因分型。采用SPSS软件分析GSTP1和GPX1基因型与临床病理特征和放疗反应的关系。结果:GPX1基因分型仅存在Pro/Pro(57.4%)和Pro/Leu(40.6%)两种基因型。C和T等位基因的等位频率分别为78.7%和21.3%。GSTP基因纯合型Val/Val和Leu/Leu分别占35.6%和12.9%。杂合型Val/Leu占51.5%。等位基因频率显示A和G两个等位基因分别在57.1%和42.9%的患者中存在。统计分析未发现GSTP Val105Ile和GPX1 Pro198Leu基因多态性与社会人口学、临床病理特征以及放疗反应之间存在显著相关性(p < 0.05)。结论:有必要进一步研究抗氧化定义基因中snp在放疗反应中的潜在作用,并确定鼻咽癌患者放射耐药的可靠预测和非侵入性生物标志物,以进行个性化治疗。肿瘤患者的基因多态性及其与放疗应答的关系
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