Heaphy Christopher M, Baumgartner Kathy B, Bisoffi Marco, Baumgartner Richard N, Griffith Jeffrey K
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-0001, USA.
Clin Cancer Res. 2007 Dec 1;13(23):7037-43. doi: 10.1158/1078-0432.CCR-07-0432.
Telomeres are nucleoprotein complexes that protect chromosome ends from degradation and recombination. Critically shortened telomeres generate genomic instability. It has been postulated that the extent of telomere DNA loss is related to the degree of genomic instability within a tumor and therefore may presage clinical outcome. The objective of this investigation was to evaluate the hypothesis that telomere DNA content (TC) in breast tumor tissues predicts breast cancer-free survival interval.
Slot blot titration assay was used to quantitate TC in 530 archival breast tumor tissues in a population-based cohort. The relationships between TC, 12 risk factors for breast cancer adverse events (i.e., death due to breast cancer, breast cancer recurrence, or development of a new primary breast tumor), and breast cancer-free survival interval were evaluated by Fisher's exact test, log-rank analysis, and univariate and multivariate Cox proportional hazards models.
TC was independent of each of the 12 risk factors. Ethnicity, tumor-node-metastasis stage, estrogen receptor, progesterone receptor, and p53 status, chemotherapy sequence, adjuvant therapy, and TC each conferred significant relative hazards. The best overall multivariate Cox proportional hazards model included TC, p53 status, tumor-node-metastasis stage, and estrogen receptor status as independent predictors of breast cancer-free survival interval (P < 0.00005). Low TC (< or =200% of standard), relative to the high-TC group (>200% of standard), conferred an adjusted relative hazard of 2.88 (95% confidence interval, 1.16-7.15; P = 0.022) for breast cancer-related adverse events.
TC in breast cancer tissue is an independent predictor in this group of breast cancer-free survival interval.
端粒是一种核蛋白复合体，可保护染色体末端免于降解和重组。端粒严重缩短会导致基因组不稳定。据推测，端粒DNA丢失的程度与肿瘤内基因组不稳定的程度相关，因此可能预示临床结果。本研究的目的是评估乳腺癌组织中端粒DNA含量（TC）可预测无乳腺癌生存间隔的假设。
采用狭缝印迹滴定法对基于人群队列中的530份存档乳腺癌组织中的TC进行定量。通过Fisher精确检验、对数秩分析以及单变量和多变量Cox比例风险模型，评估TC、12种乳腺癌不良事件风险因素（即因乳腺癌死亡、乳腺癌复发或新发原发性乳腺癌）与无乳腺癌生存间隔之间的关系。
TC与12种风险因素中的每一种均无关。种族、肿瘤-淋巴结-转移分期、雌激素受体、孕激素受体、p53状态、化疗顺序、辅助治疗以及TC各自均具有显著的相对风险。最佳的总体多变量Cox比例风险模型包括TC、p53状态、肿瘤-淋巴结-转移分期和雌激素受体状态，作为无乳腺癌生存间隔的独立预测因素（P < 0.00005）。相对于高TC组（>标准值的200%），低TC（≤标准值的200%）与乳腺癌相关不良事件的校正相对风险为2.88（95%置信区间，1.16 - 7.15；P = 0.022）。
乳腺癌组织中的TC是该组无乳腺癌生存间隔的独立预测因素。
