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Genetic Variability of Antioxidative Mechanisms and Cardiotoxicity after Adjuvant Radiotherapy in HER2-Positive Breast Cancer Patients
Disease Markers Pub Date : 2020-12-22 , DOI: 10.1155/2020/6645588
Tanja Marinko 1, 2 , Jakob Timotej Stojanov Konda 2 , Vita Dolžan 3 , Katja Goričar 3
Affiliation  

Background. Breast cancer treatment is associated with the occurrence of various cardiac adverse events. One of the mechanisms associated with cardiotoxicity is oxidative stress, against which cells are protected by antioxidative enzymes. Genetic variability of antioxidative enzymes can affect enzyme activity or expression, which modifies the ability of cells to defend themselves against oxidative stress and could consequently contribute to the occurrence of treatment-related cardiotoxicity. Our aim was to evaluate the association of common polymorphisms in antioxidative genes with cardiotoxicity after adjuvant radiotherapy (RT) in HER2-positive breast cancer patients. Methods. Our retrospective study included 101 HER2-positive early breast cancer patients who received trastuzumab and adjuvant RT. We isolated DNA from buccal swabs and used competitive allele-specific PCR for genotyping of PON1 rs854560 and rs662, GSTP1 rs1138272 and rs1695, SOD2 rs4880, CAT rs1001179, and HIF1 rs1154965 polymorphisms. N-terminal pro B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction, and NYHA class were used as markers of cardiotoxicity. We used logistic regression to evaluate the association of genetic factors with markers of cardiotoxicity. Results. Carriers of at least one polymorphic PON1 rs854560 allele were less likely to have increased NT-proBNP (; 95% CI = 0.15-0.79; ), even after adjustment for age (; 95% CI = 0.15-0.83; ). Carriers of at least one polymorphic PON1 rs662 allele were more likely to have increased NT-proBNP (; 95% CI = 1.85-10.66; ), even after adjustment for age (; 95% CI = 2.12-13.78; ). GSTP1 rs1695 was also associated with decreased NT-proBNP in the multivariable analysis (), while CAT rs1001179 was associated with NYHA class in the univariable () and multivariable analysis (). Conclusion. In our study, polymorphisms PON1 rs662 and rs854560, CAT rs1001179, and GSTP1 rs1695 were significantly associated with the occurrence of cardiac adverse events after adjuvant RT and could serve as biomarkers contributing to treatment personalization.

中文翻译:

HER2阳性乳腺癌患者辅助放疗后抗氧化机制和心脏毒性的遗传变异

背景。乳腺癌治疗与各种心脏不良事件的发生有关。与心脏毒性相关的机制之一是氧化应激,细胞受到抗氧化酶的保护。抗氧化酶的遗传变异性会影响酶的活性或表达,从而改变细胞抵御氧化应激的能力,从而导致与治疗相关的心脏毒性的发生。我们的目的是评估抗氧化基因的常见多态性与 HER2 阳性乳腺癌患者辅助放疗 (RT) 后心脏毒性的关系。方法. 我们的回顾性研究包括 101 名接受曲妥珠单抗和辅助放疗的 HER2 阳性早期乳腺癌患者。我们从口腔拭子中分离 DNA,并使用竞争性等位基因特异性 PCR 对PON1 rs854560 和 rs662、GSTP1 rs1138272 和 rs1695、SOD2 rs4880、CAT rs1001179 和HIF1 rs1154965 多态性进行基因分型。N-末端前B型利钠肽(NT-proBNP)、左心室射血分数和NYHA类被用作心脏毒性的标志物。我们使用逻辑回归来评估遗传因素与心脏毒性标志物的关联。结果。至少一种多态PON1的载体rs854560 等位基因不太可能增加 NT-proBNP (; 95% CI = 0.15-0.79;),即使在调整了年龄后 (; 95% CI = 0.15-0.83;)。至少一个多态性PON1 rs662 等位基因的携带者更有可能增加 NT-proBNP(; 95% CI = 1.85-10.66;),即使在调整了年龄后 (; 95% CI = 2.12-13.78;)。 在多变量分析中, GSTP1 rs1695 也与 NT-proBNP 降低有关(),CAT rs1001179 在单变量 ()和多变量分析 ()。 结论。在我们的研究中,多态性PON1 rs662 和 rs854560、 CAT rs1001179 和GSTP1 rs1695 与辅助放疗后心脏不良事件的发生显着相关,可作为有助于治疗个性化的生物标志物。
更新日期:2020-12-22
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