Department of Medical Genetics, Third Faculty of Medicine, Charles University, Prague 100 00, Czech Republic.
Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague 142 00, Czech Republic.
Oncol Rep. 2020 Nov;44(5):2219-2230. doi: 10.3892/or.2020.7774. Epub 2020 Sep 21.
Accumulation of non‑specific structural chromosomal aberrations (CAs) and telomere shortening contribute to genome instability, which constitutes as one of the hallmarks of cancer. CAs arise due to direct DNA damage or telomere shortening. CAs in peripheral blood lymphocytes (PBL), which are considered to be markers of exposure, have been previously reported to serve a role in the pathophysiology and progression of cancer through mechanisms that are poorly understood. In addition, the prognostic relevance of telomere length (TL) in patients with cancer remains to be elucidated. In the present study, CAs and TL in PBL isolated from patients with newly diagnosed cancer (151 breast, 96 colorectal, 90 lung) and 335 cancer‑free control individuals were investigated. These results were then correlated with clinicopathological factors and follow‑up data. The accumulation of CAs in PBL was observed with increased susceptibility to breast and lung cancer (P<0.0001), while individuals with longer TL were found to be at a higher risk of breast cancer (P<0.0001). Increased chromatid‑type aberrations were also revealed to be associated with lower overall survival of patients with breast and colorectal cancers using a multivariate model. Compared with control individuals, no association was observed between TL and CAs or age in patients with cancer. In conclusion, the present study demonstrates the association between CAs/TL in PBL and the susceptibility, prognosis and survival of patients with breast, colorectal and lung cancer.
非特异性结构染色体畸变 (CAs) 和端粒缩短的积累导致基因组不稳定,这是癌症的标志之一。CAs 是由于直接的 DNA 损伤或端粒缩短而产生的。外周血淋巴细胞 (PBL) 中的 CAs 被认为是暴露的标志物,先前的研究报道称,它们通过机制在癌症的病理生理学和进展中发挥作用,但这些机制仍不清楚。此外,癌症患者端粒长度 (TL) 的预后相关性仍有待阐明。在本研究中,研究了新诊断癌症患者(151 例乳腺癌、96 例结直肠癌、90 例肺癌)和 335 例无癌症对照个体的 PBL 中的 CAs 和 TL。然后将这些结果与临床病理因素和随访数据相关联。观察到 PBL 中的 CAs 积累与乳腺癌和肺癌的易感性增加有关(P<0.0001),而 TL 较长的个体患乳腺癌的风险更高(P<0.0001)。使用多变量模型还发现,增加的染色单体型畸变与乳腺癌和结直肠癌患者的总生存率降低有关。与对照组个体相比,在癌症患者中,TL 与 CAs 或年龄之间未观察到相关性。总之,本研究表明 PBL 中的 CAs/TL 与乳腺癌、结直肠癌和肺癌患者的易感性、预后和生存相关。