Butkiewicz Dorota, Krześniak Małgorzata, Gdowicz-Kłosok Agnieszka, Składowski Krzysztof, Rutkowski Tomasz
Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland.
I Radiation and Clinical Oncology Department, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland.
Cancers (Basel). 2023 Oct 13;15(20):4972. doi: 10.3390/cancers15204972.
Radiotherapy and cisplatin-based chemotherapy belong to the main treatment modalities for head and neck squamous cell carcinoma (HNSCC) and induce cancer cell death by generating DNA damage, including the most severe double-strand breaks (DSBs). Alterations in DSB response and repair genes may affect individual DNA repair capacity and treatment sensitivity, contributing to the therapy resistance and poor prognosis often observed in HNSCC. In this study, we investigated the association of a panel of single-nucleotide polymorphisms (SNPs) in 20 DSB signaling and repair genes with therapy results and prognosis in 505 HNSCC patients treated non-surgically with DNA damage-inducing therapies. In the multivariate analysis, there were a total of 14 variants associated with overall, locoregional recurrence-free or metastasis-free survival. Moreover, we identified 10 of these SNPs as independent predictors of therapy failure and unfavorable prognosis in the whole group or in two treatment subgroups. These were rs2155209, rs828907, rs1801321, rs12593359, rs1805388, rs558351, rs1042522, rs1801516, rs2267437 and rs2735383. Only rs558351 remained statistically significant after correcting for multiple testing. These results suggest that specific germline variants related to DSB response and repair may be potential genetic modifiers of therapy effects and disease progression in HNSCC treated with radiotherapy and cisplatin-based chemoradiation.
放射治疗和顺铂化疗是头颈部鳞状细胞癌（HNSCC）的主要治疗方式，它们通过产生DNA损伤（包括最严重的双链断裂DSB）来诱导癌细胞死亡。DSB反应和修复基因的改变可能会影响个体的DNA修复能力和治疗敏感性，导致HNSCC中常见的治疗抵抗和预后不良。在本研究中，我们调查了20个DSB信号传导和修复基因中的一组单核苷酸多态性（SNP）与505例接受DNA损伤诱导疗法的非手术HNSCC患者的治疗结果和预后之间的关联。在多变量分析中，共有14个变体与总生存期、局部区域无复发生存期或无转移生存期相关。此外，我们确定其中10个SNP是整个组或两个治疗亚组中治疗失败和不良预后的独立预测因子。这些SNP分别是rs2155209、rs828907、rs1801321、rs12593359、rs1805388、rs558351、rs1042522、rs1801516、rs2267437和rs2735383。在进行多重检验校正后，只有rs558351仍具有统计学意义。这些结果表明，与DSB反应和修复相关的特定种系变体可能是接受放疗和顺铂化疗的HNSCC治疗效果和疾病进展的潜在遗传修饰因子。
