Cuchra Magda, Mucha Bartosz, Markiewicz Lukasz, Przybylowska-Sygut Karolina, Pytel Dariusz, Jeziorski Arkadiusz, Kordek Radzisław, Majsterek Ireneusz
Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.
Mol Carcinog. 2016 Dec;55(12):1899-1914. doi: 10.1002/mc.22436. Epub 2015 Nov 19.
Breast cancer (BC) is leading type of cancer among group of women, which determines almost 23% of invasive cancers. It has been reported repeatedly that the level of oxidative stress is higher for BC in comparison to cancer-free woman. The goal of the present study was to evaluate the role of base excision repair (BER) pathway in the development of BC. One-hundred seventy-one women with confirmed BC and 222 healthy controls were enrolled in presented study. The level of oxidative DNA damage and the kinetic of their repair were analyzed by the modified alkaline comet assay. The efficiency of BER pathway was evaluated by BER assay. The presence of the 326Cys/Cys genotype and 326Cys allele of OGG1 gene and the 324His/His of MUTYH gene are associated with increased risk of BC development. Moreover, correlation between clinical parameter with selected genes has shown increased risk of BC progression. The survival analysis has shown a significant lower DFS for individuals with the 762Ala/Ala genotype compared to 762Val/Vla carriers and the 762Val/Ala genotype in relation to concomitant chemotherapy and radiotherapy. In subgroup of patients with alone chemotherapy and alone radiotherapy, the 762Val/Val genotype was significantly associated with lower overall survival. Furthermore, we also elevated the level of basal and oxidative DNA damage in a group of patients with BC in relation to healthy controls. We also observed the difference in effectiveness of DNA damage repair. The results of present studies suggested the important role of BER pathway in BC development. © 2015 Wiley Periodicals, Inc.
乳腺癌（BC）是女性群体中最主要的癌症类型，约占侵袭性癌症的23%。多次报道显示，与未患癌女性相比，乳腺癌患者的氧化应激水平更高。本研究的目的是评估碱基切除修复（BER）途径在乳腺癌发生发展中的作用。本研究纳入了171例确诊为乳腺癌的女性和222例健康对照。采用改良碱性彗星试验分析氧化DNA损伤水平及其修复动力学。通过BER试验评估BER途径的效率。OGG1基因的326Cys/Cys基因型和326Cys等位基因以及MUTYH基因的324His/His与乳腺癌发生风险增加相关。此外，临床参数与所选基因之间的相关性显示乳腺癌进展风险增加。生存分析表明，与762Val/Vla携带者和762Val/Ala基因型相比，762Ala/Ala基因型个体在接受同步化疗和放疗时的无病生存期显著缩短。在单独接受化疗和单独接受放疗的患者亚组中，762Val/Val基因型与较低的总生存期显著相关。此外，与健康对照相比，我们还发现一组乳腺癌患者的基础和氧化DNA损伤水平升高。我们还观察到DNA损伤修复效率的差异。本研究结果提示BER途径在乳腺癌发生发展中起重要作用。© 2015威利期刊公司
