铂类化疗对晚期非小细胞肺癌（NSCLC）患者的不良事件是主要挑战。在这项研究中,我们研究了p53和MDM2基因在预测接受铂类化疗的NSCLC患者不良事件中的作用.具体来说,我们检查了p53p。Pro72Arg（rs1042522），MDM2c.14+309T>G(rs2279744)和MDM2c-461C>G(rs937282)多态性使用基于PCR的限制性片段长度多态性(RFLP)在444例NSCLC患者中。我们确定MDM2c.14+309T>G与铂类化疗治疗的晚期NSCLC患者的严重血液学和总体毒性显著相关。特别是57岁及以下的患者。对于腺癌患者也是如此。第二,我们确定杂合子MDM2c-461C>G患者的严重胃肠道毒性明显高于G/G基因型患者.第三，MDM2c-461C>G-c.14309T>GCT单倍型的患者比CG单倍型的患者表现出更高的毒性。此外，携带MDM2c.-461>G-c.14309T>GCG/CT复型的患者比携带CG/CG的患者表现出更高的毒性。第四，我们发现p53p。Pro72Arg多态性与年龄和基因型相互作用。此外,在晚期NSCLC患者中,3个SNPs与一线铂类化疗的疗效无显著关联.总之,我们发现p53p.Pro72Arg,MDM2c.14+309T>G和MDM2c-461C>G多态性与晚期NSCLC患者铂类化疗后的毒性风险相关。我们建议MDM2c.14+309T>G可用作预测铂类化疗晚期NSCLC患者不良事件的候选生物标志物。
Adverse events in platinum-based chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) are major challenges. In this study, we investigated the role of the p53 and MDM2 genes in predicting adverse events in NSCLC patients treated with platinum-based chemotherapy. Specifically, we examined the p53 p. Pro72Arg (rs1042522), MDM2 c.14 + 309T>G (rs2279744) and MDM2 c.- 461C > G (rs937282) polymorphisms using PCR-based restriction fragment length polymorphism (RFLP) in 444 NSCLC patients. We determine that MDM2 c.14 + 309T > G was significantly associated with severe hematologic and overall toxicities for advanced NSCLC patients treated with platinum-based chemotherapy, especially for patients aged 57 and younger. This was also true for patients with adenocarcinoma. Second, we determine that severe gastrointestinal toxicities in patients with heterozygous MDM2 c.-461C > G were significantly higher than in patients with the G/G genotype. Third, patients with the MDM2 c.-461C > G - c.14 + 309T > G CT haplotype show much higher toxicities than those of CG haplotype. Moreover, patients carrying the MDM2 c.-461 > G -c.14 + 309T > G CG/CT diplotype exhibited higher toxicities than those carrying CG/CG. Fourth, we found that the p53 p. Pro72Arg polymorphism interacts with both age and genotype. In addition, no significant associations were observed between the 3 SNPs and the response to first-line platinum-based chemotherapy in advanced NSCLC patients. In summary, we found that the p53 p. Pro72Arg, MDM2 c.14 + 309T > G and MDM2 c.-461C > G polymorphisms are associated with toxicity risks following platinum-based chemotherapy treatment in advanced NSCLC patients. We suggest that MDM2 c.14 + 309T > G may be used as a candidate biomarker to predict adverse events in advanced NSCLC patients who had platinum-based chemotherapy treatment.
