Goričar Katja, Dugar Franja, Dolžan Vita, Marinko Tanja
Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Cancers (Basel). 2022 Sep 8;14(18):4365. doi: 10.3390/cancers14184365.
Radiotherapy (RT) for breast cancer significantly impacts patient survival and causes adverse events. Double-strand breaks are the most harmful type of DNA damage associated with RT, which is repaired through homologous recombination (HRR). As genetic variability of DNA repair genes could affect response to RT, we aimed to evaluate the association of polymorphisms in HRR genes with tumor characteristics and the occurrence of RT adverse events in early HER2-positive breast cancer. Our study included 101 breast cancer patients treated with adjuvant RT and trastuzumab. All patients were genotyped for eight single nucleotide polymorphisms in , and using competitive allele-specific PCR. Carriers of rs1799794 GG genotype were less likely to have higher tumor differentiation grade (OR = 0.05, 95% CI = 0.01-0.44, = 0.007). Carriers of rs1801321 TT genotype were more likely to have higher NYHA class in univariable (OR = 10.0; 95% CI = 1.63-61.33; = 0.013) and multivariable (OR = 9.27; 95% CI = 1.28-67.02; = 0.027) analysis. Carriers of rs12593359 GG genotype were less likely to have higher NYHA class in univariable (OR = 0.09; 95% CI = 0.01-0.79; = 0.030) and multivariable (OR = 0.07; 95% CI = 0.01-0.81; = 0.034) analysis. Carriers of rs1799794 GG genotypes experienced more skin adverse events based on LENT-SOMA scale in univariable (OR = 5.83; 95% CI = 1.22-28.00; = 0.028) and multivariable (OR = 10.90; 95% CI = 1.61-73.72; = 0.014) analysis. In conclusion, and polymorphisms might contribute to RT adverse events in early HER2-positive breast cancer patients.
乳腺癌放疗（RT）对患者生存有显著影响并会引发不良事件。双链断裂是与放疗相关的最有害的DNA损伤类型，可通过同源重组（HRR）进行修复。由于DNA修复基因的遗传变异性可能影响对放疗的反应，我们旨在评估HRR基因多态性与早期HER2阳性乳腺癌患者肿瘤特征及放疗不良事件发生之间的关联。我们的研究纳入了101例接受辅助放疗和曲妥珠单抗治疗的乳腺癌患者。使用竞争性等位基因特异性PCR对所有患者的 、 和 中的8个单核苷酸多态性进行基因分型。rs1799794 GG基因型携带者肿瘤分化程度较高的可能性较小（OR = 0.05，95%CI = 0.01 - 0.44， = 0.007）。在单变量分析（OR = 10.0；95%CI = 1.63 - 61.33； = 0.013）和多变量分析（OR = 9.27；95%CI = 1.28 - 67.02； = 0.027）中，rs1801321 TT基因型携带者纽约心脏协会（NYHA）分级较高的可能性更大。在单变量分析（OR = 0.09；95%CI = 0.01 - 0.79； = 0.030）和多变量分析（OR = 0.07；95%CI = 0.01 - 0.81； = 0.034）中，rs12593359 GG基因型携带者NYHA分级较高的可能性较小。根据LENT - SOMA量表，在单变量分析（OR = 5.83；95%CI = 1.22 - 28.00； = 0.028）和多变量分析（OR = 10.90；95%CI = 1.61 - 73.72； = 0.014）中，rs1799794 GG基因型携带者出现更多皮肤不良事件。总之， 和 基因多态性可能与早期HER2阳性乳腺癌患者的放疗不良事件有关。
