XPD 和 TP53 基因多态性对孟加拉国肺癌患者铂类化疗诱导毒性风险的影响。
Effect of XPD and TP53 Gene Polymorphisms on the Risk of Platinum-Based Chemotherapy Induced Toxicity in Bangladeshi Lung Cancer Patients.
机构信息
Department of Biochemistry and Molecular Biology, Noakhali Science and Technology University, Bangladesh.
Department of Pharmacy, Manarat International University, Bangladesh.
出版信息
Asian Pac J Cancer Prev. 2021 Dec 1;22(12):3809-3815. doi: 10.31557/APJCP.2021.22.12.3809.
BACKGROUND
Platinum-based drugs, including cisplatin and carboplatin, are the most active and extensively used agents for treating lung cancer. Genetic polymorphisms of DNA repair gene XPD and tumor suppressor gene TP53 are connected with alterations in enzyme activity. They may help explain interindividual differences in toxicity outcomes after platinum-based chemotherapy for lung cancer. Therefore, this study aimed to investigate XPD Lys751Gln and TP53 Arg72Pro polymorphisms on the risk of platinum-based chemotherapy-induced toxicity in lung cancer patients in the Bangladeshi population.
PATIENTS AND METHODS
Study subjects comprised of 180 platinum-based chemotherapy treated histologically confirmed lung cancer patients. Genetic polymorphisms of XPD were ascertained by Polymerase Chain Reaction-based Restriction Fragment Length Polymorphism (PCR-RFLP), while TP53 genotypes were analyzed using the multiplex PCR-based method. Toxicity was assessed based on the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
RESULTS
From the results, there was no significant association observed between grade 1-2 or grade 3-4 platinum-based chemotherapy induced toxicities like anemia and XPD codon 751 (Lys/Gln: OR=1.40, 95% CI=0.75-2.64, p>0.05; Gln/Gln: OR=1.07, 95% CI=0.45-2.52, p>0.05 and Lys/Gln+Gln/Gln: OR=1.31, 95% CI=0.73-2.38, p>0.05) or TP53 codon 72 genetic polymorphisms (Arg/Pro: OR=0.64, 95% CI=0.34-1.17, p>0.05; Pro/Pro: OR=0.46, 95% CI=0.15-1.42, p>0.05 and Arg/Pro+Pro/Pro: OR=0.62, 95% CI=0.34-1.15, p>0.05). Similar results were found between neutropenia, leukopenia, thrombocytopenia and gastrointestinal toxicities and XPD Lys751Gln or TP53 Arg72Pro genetic polymorphisms.
CONCLUSION
These findings indicated that no significant association was found between either XPD codon 751 or TP53 codon 72 genetic polymorphisms and platinum-based chemotherapy-related toxicities in Bangladeshi lung cancer patients.
背景
铂类药物，包括顺铂和卡铂，是治疗肺癌最有效和广泛使用的药物。DNA 修复基因 XPD 和肿瘤抑制基因 TP53 的遗传多态性与酶活性的改变有关。它们可能有助于解释肺癌铂类化疗后个体间毒性结局的差异。因此，本研究旨在探讨孟加拉国人群中 XPD Lys751Gln 和 TP53 Arg72Pro 多态性与铂类化疗诱导的肺癌毒性的关系。
患者和方法
本研究纳入了 180 名接受组织学证实的肺癌铂类化疗的患者。XPD 多态性通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）确定，而 TP53 基因型则采用多重 PCR 法分析。毒性根据常见不良事件术语标准（CTCAE v5.0）进行评估。
结果
结果显示，XPD 密码子 751（Lys/Gln：OR=1.40，95%CI=0.75-2.64，p>0.05；Gln/Gln：OR=1.07，95%CI=0.45-2.52，p>0.05 和 Lys/Gln+Gln/Gln：OR=1.31，95%CI=0.73-2.38，p>0.05）或 TP53 密码子 72 遗传多态性（Arg/Pro：OR=0.64，95%CI=0.34-1.17，p>0.05；Pro/Pro：OR=0.46，95%CI=0.15-1.42，p>0.05 和 Arg/Pro+Pro/Pro：OR=0.62，95%CI=0.34-1.15，p>0.05）与铂类化疗诱导的 1-2 级或 3-4 级毒性（贫血）之间无显著相关性。中性粒细胞减少症、白细胞减少症、血小板减少症和胃肠道毒性与 XPD Lys751Gln 或 TP53 Arg72Pro 遗传多态性之间也存在类似的关系。
结论
这些发现表明，在孟加拉国肺癌患者中，XPD 密码子 751 或 TP53 密码子 72 遗传多态性与铂类化疗相关毒性之间无显著相关性。
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