Abstract

Disruption of telomere length (TL) homeostasis in peripheral blood lymphocytes has been previously assessed as a potential biomarker of breast cancer (BC) risk. The present study addressed the relationship between lymphocyte TL (LTL), prognosis and clinicopathological features in the BC patients since these associations are insufficiently explored at present. LTL was measured in 611 BC patients and 154 healthy controls using the monochrome multiplex quantitative Polymerase Chain Reaction assay. In addition, we genotyped nine TL-associated single-nucleotide polymorphisms that had been identified through genome-wide association studies. Our results showed that the patients had significantly (P = 0.001, Mann–Whitney U-test) longer LTL [median (interquartile range); 1.48 (1.22–1.78)] than the healthy controls [1.27 (0.97–1.82)]. Patients homozygous (CC) for the common allele of hTERT rs2736108 or the variant allele (CC) of hTERC rs16847897 had longer LTL. The latter association remained statistically significant in the recessive genetic model after the Bonferroni correction (P = 0.004, Wilcoxon two-sample test). We observed no association between LTL and overall survival or relapse-free survival of the patients. LTL did not correlate with cancer staging based on Union for International Cancer Control (UICC), The tumor node metastasis (TNM) staging system classification, tumour grade or molecular BC subtypes. Overall, we observed an association between long LTL and BC disease and an association of the hTERC rs16847897 CC genotype with increased LTL. However, no association between LTL, clinicopathological features and survival of the patients was found.

中文翻译：

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乳腺癌患者外周血淋巴细胞端粒长度与端粒酶遗传变异、预后及临床病理特征相关

摘要

外周血淋巴细胞端粒长度 (TL) 稳态的破坏先前已被评估为乳腺癌 (BC) 风险的潜在生物标志物。本研究探讨了 BC 患者淋巴细胞 TL (LTL)、预后和临床病理特征之间的关系，因为目前这些关联尚未得到充分探索。使用单色多重定量聚合酶链反应测定法测量了 611 名 BC 患者和 154 名健康对照的 LTL。此外，我们对通过全基因组关联研究确定的 9 个与 TL 相关的单核苷酸多态性进行了基因分型。我们的结果表明，患者有显着（P = 0.001，Mann-Whitney U-test）更长的 LTL [中位数（四分位距）；1.48 (1.22–1.78)] 比健康对照 [1.27 (0.97–1.82)]。hTERT rs2736108的共同等位基因或hTERC rs16847897的变异等位基因 (CC)纯合子 (CC) 的患者具有更长的 LTL。后一种关联在 Bonferroni 校正后的隐性遗传模型中仍然具有统计学意义（P= 0.004，Wilcoxon 双样本检验）。我们观察到 LTL 与患者的总生存期或无复发生存期之间没有关联。LTL 与基于国际癌症控制联盟 (UICC)、肿瘤淋巴结转移 (TNM) 分期系统分类、肿瘤分级或分子 BC 亚型的癌症分期无关。总体而言，我们观察到长 LTL 和 BC 疾病之间的关联以及hTERC rs16847897 CC 基因型与 LTL 增加的关联。然而，未发现 LTL、临床病理特征和患者存活率之间存在关联。