DNA修复基因的遗传多态性及其对乳腺癌患者紫杉醇化疗诱导毒性反应的影响。
Genetic Polymorphisms of DNA Repair Genes and their Influence on Paclitaxel based Chemotherapy Induced Toxicity Reactions in Breast Cancer Patients.
作者信息
Datkhile Kailas D, Reur Prajakta N, Kale Shivani R, Gudur Rashmi A, Bhosale Suresh J, Gudur Anand K
机构信息
Department of Molecular Biology & Genetics, Krishna Institute of Allied Sciences, Krishna Vishwa Vidyapeeth (Deemed to be University), Taluka-Karad, Dist- Satara, Pin-415 539, (Maharashtra) India.
Department of Oncology, Krishna Vishwa Vidyapeeth "Deemed to be University", Taluka-Karad, Dist- Satara, Pin-415 539, (Maharashtra) India.
出版信息
Asian Pac J Cancer Prev. 2024 Dec 1;25(12):4281-4292. doi: 10.31557/APJCP.2024.25.12.4281.
BACKGROUND
Systemic chemotherapy constitutes an indispensable component of breast cancer (BC) management, where therapeutic drug combinations such as anthracyclines, platinum compounds, and taxanes form the cornerstone of standard treatment protocols. Although DNA repair genes are pivotal in cancer susceptibility, their specific roles in mediating acute or chronic toxicity outcomes induced by chemotherapy remain undetermined. Consequently, this study was planned to elucidate the impact of polymorphisms in base excision repair (BER) genes, including XRCC1, XRCC2, XRCC3, APE1, and hOGG1, on treatment response and toxicity outcomes in BC patients undergoing paclitaxel and doxorubicin-based chemotherapy within an Indian population.
METHODS
One hundred and four (104) BC patients receiving combined paclitaxel and doxorubicin chemotherapy were enrolled with documentation of both hematological and non-hematological toxicity reactions induced by the treatment. Genetic polymorphism of XRCC1, XRCC2, XRCC3, APE1, and hOGG1 genes was investigated using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) analysis.
RESULTS
Analysis of the demographic characteristics of BC patients revealed a significant association between mucositis and peripheral neuropathy with advancing age. An increased body mass index was also significantly correlated with hematological toxicities, such as neutropenia (p=0.022) and febrile neutropenia (p=0.048), as well as with peripheral neuropathy (p=0.001). Univariate logistic regression analysis demonstrated a significant association between the XRCC3 (Ser241Cys) polymorphism and peripheral neuropathy (OR=3.00, 95% CI: 1.29-6.95; p=0.010). Similarly, regression analysis indicated a significant association of APE-1 (Asp148Glu) polymorphism with febrile neutropenia (OR=3.55, 95% CI: 1.03-12.21; p=0.044) and chemotherapy-induced nausea and vomiting (CINV) (OR=4.19, 95% CI: 1.61-10.94; p=0.003) in BC patients treated with paclitaxel and Doxorubicin regimen.
CONCLUSION
The findings from this study underscore the significant influence of genetic polymorphisms in XRCC3 (Ser241Cys) and APE-1 (Asp148Glu) on the acute toxicity effects induced by paclitaxel in BC patients.
背景
全身化疗是乳腺癌（BC）治疗中不可或缺的组成部分，其中蒽环类、铂类化合物和紫杉烷类等治疗药物组合构成了标准治疗方案的基石。尽管DNA修复基因在癌症易感性中起关键作用，但其在介导化疗引起的急性或慢性毒性结果中的具体作用仍未确定。因此，本研究旨在阐明碱基切除修复（BER）基因（包括XRCC1、XRCC2、XRCC3、APE1和hOGG1）的多态性对印度人群中接受基于紫杉醇和阿霉素化疗的BC患者治疗反应和毒性结果的影响。
方法
招募了104例接受紫杉醇和阿霉素联合化疗的BC患者，并记录了治疗引起的血液学和非血液学毒性反应。采用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析研究XRCC1、XRCC2、XRCC3、APE1和hOGG1基因的遗传多态性。
结果
对BC患者的人口统计学特征分析显示，粘膜炎和周围神经病变与年龄增长显著相关。体重指数增加也与血液学毒性（如中性粒细胞减少（p = 0.022）和发热性中性粒细胞减少（p = 0.048））以及周围神经病变（p = 0.001）显著相关。单因素逻辑回归分析表明，XRCC3（Ser241Cys）多态性与周围神经病变之间存在显著关联（OR = 3.00，95% CI：1.29 - 6.95；p = 0.010）。同样，回归分析表明，APE - 1（Asp148Glu）多态性与接受紫杉醇和阿霉素方案治疗的BC患者的发热性中性粒细胞减少（OR = 3.55，95% CI：1.03 - 12.21；p = 0.044）和化疗引起的恶心和呕吐（CINV）（OR = 4.19，95% CI：1.61 - 10.94；p = 0.003）显著相关。
结论
本研究结果强调了XRCC3（Ser241Cys）和APE - 1（Asp148Glu）基因多态性对BC患者紫杉醇诱导的急性毒性作用的显著影响。
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