Division of Epidemiology, Mayo Clinic, Jacksonville, Florida.
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Cancer Epidemiol Biomarkers Prev. 2021 Jan;30(1):210-216. doi: 10.1158/1055-9965.EPI-20-1279. Epub 2020 Nov 13.
Critically shortened telomeres contribute to chromosomal instability and neoplastic transformation and are associated with early death of patients with certain cancer types. Shorter leukocyte telomere length (LTL) has been associated with higher risk for pancreatic ductal adenocarcinoma (PDAC) and might be associated also with survival of patients with PDAC. We investigated the association between treatment-naïve LTL and overall survival of patients with incident PDAC.
The study included 642 consecutively enrolled PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreas Research. Blood samples were obtained at the time of diagnosis, before the start of cancer treatment, from which LTL was assayed by qRT-PCR. LTL was first modeled as a continuous variable (per-interquartile range decrease in LTL) and then as a categorized variable (short, medium, long). Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated for overall mortality using Cox proportional hazard models.
Shorter treatment-naïve LTL was associated with higher mortality among patients with PDAC (HR = 1.13, 95% CI: 1.01-1.28, = 0.03; HR = 1.29, 95% CI: 1.05-1.59, = 0.01). There was a difference in the association between LTL and overall mortality by tumor stage at diagnosis; resectable tumors (HR = 0.91; 95% CI: 0.73-1.12), locally advanced tumors (HR = 1.29; 95% CI: 1.07-1.56), and metastatic tumors (HR = 1.17; 95% CI: 0.96-1.42), = 0.04.
Shorter treatment-naïve LTL is associated with poorer overall survival of patients with incident PDAC.
Peripheral blood LTL might be a prognostic marker for PDAC.
端粒的严重缩短会导致染色体不稳定和肿瘤转化，并与某些癌症类型患者的早逝有关。白细胞端粒长度（LTL）较短与胰腺导管腺癌（PDAC）的风险增加有关，并且可能与 PDAC 患者的生存有关。我们研究了未经治疗的 LTL 与新发 PDAC 患者总生存率之间的关系。
本研究纳入了梅奥诊所生物样本资源库中 642 例连续入组的 PDAC 患者。在诊断时，即在开始癌症治疗之前，从这些患者的血液样本中提取 LTL 并通过 qRT-PCR 进行检测。首先，将 LTL 建模为连续变量（LTL 每降低一个四分位间距），然后建模为分类变量（短、中、长）。使用 Cox 比例风险模型计算总体死亡率的多变量调整 HR 和 95%CI。
未经治疗的 LTL 较短与 PDAC 患者的死亡率较高相关（HR = 1.13，95%CI：1.01-1.28，P = 0.03；HR = 1.29，95%CI：1.05-1.59，P = 0.01）。LTL 与总体死亡率之间的关系因诊断时的肿瘤分期而有所不同；可切除肿瘤（HR = 0.91；95%CI：0.73-1.12）、局部进展期肿瘤（HR = 1.29；95%CI：1.07-1.56）和转移性肿瘤（HR = 1.17；95%CI：0.96-1.42），P = 0.04。
未经治疗的 LTL 较短与新发 PDAC 患者的总体生存率较差相关。
外周血 LTL 可能是 PDAC 的预后标志物。
