Genetic Polymorphisms of DNA Repair Genes and their Influence on Paclitaxel based Chemotherapy Induced Toxicity Reactions in Breast Cancer Patients.

Q2 Medicine

Asian Pacific Journal of Cancer Prevention Pub Date : 2024-12-01 DOI:10.31557/APJCP.2024.25.12.4281

Kailas D Datkhile, Prajakta N Reur, Shivani R Kale, Rashmi A Gudur, Suresh J Bhosale, Anand K Gudur

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引用次数: 0

Abstract

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.

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乳腺癌患者 DNA 修复基因的遗传多态性及其对紫杉醇类化疗引起的毒性反应的影响

背景：全身化疗是乳腺癌治疗不可或缺的组成部分，其中蒽环类药物、铂类化合物和紫杉烷等治疗药物组合是标准治疗方案的基石。尽管DNA修复基因在癌症易感性中起着关键作用，但它们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，本研究计划阐明碱基切除修复（BER）基因多态性，包括XRCC1、XRCC2、XRCC3、APE1和hOGG1，对印度人群中接受紫杉醇和阿霉素化疗的BC患者的治疗反应和毒性结果的影响。方法：104例接受紫杉醇联合阿霉素化疗的BC患者，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XRCC1、XRCC2、XRCC3、APE1和hOGG1基因的遗传多态性。结果：对BC患者人口学特征的分析显示，随着年龄的增长，粘膜炎和周围神经病变之间存在显著关联。体重指数的增加也与血液毒性显著相关，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）。单因素logistic回归分析显示，XRCC3 （Ser241Cys）多态性与周围神经病变之间存在显著相关性(OR=3.00, 95% CI: 1.29-6.95；p = 0.010)。同样，回归分析显示，APE-1 （Asp148Glu）多态性与发热性中性粒细胞减少症有显著相关性(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)。结论：本研究结果强调了XRCC3 （Ser241Cys）和ape1 （Asp148Glu）基因多态性对BC患者紫杉醇急性毒性作用的显著影响。

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来源期刊

Asian Pacific Journal of Cancer Prevention 医学-肿瘤学

CiteScore

2.80

自引率

0.00%

发文量

779

审稿时长

3 months

期刊介绍： Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: -Epidemiology, detection and screening. -Cellular research and bio-markers. -Identification of bio-targets and agents with novel mechanisms of action. -Optimal clinical use of existing anti-cancer agents, including combination therapies. -Radiation and surgery. -Palliative care. -Patient adherence, quality of life, satisfaction. -Health economic evaluations.