Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Hum Mol Genet. 2011 Jan 15;20(2):378-86. doi: 10.1093/hmg/ddq461. Epub 2010 Oct 18.
Although telomere dysfunction is a characteristic of breast cancer cells, the relationship between deficiency on individual chromosomal telomeres in normal somatic cells and breast cancer risk has not been characterized. A case-control study was conducted to examine the associations between individual lengths of 92 telomeres in the human genome and the risk of breast cancer in 204 newly diagnosed breast cancer patients and 236 healthy controls. Chromosome arm-specific telomere lengths were measured by telomere quantitative fluorescent in situ hybridization. Unconditional logistic regression was used to estimate the risk associations. This genome-wide screen identified that shorter telomere lengths on chromosomes Xp and 15p were associated with breast cancer risk in pre-menopausal women, with adjusted odds ratios (aORs) of 2.5 (95% CI = 1.3, 4.8) and 2.6 (1.3, 5.0), respectively. The study also revealed that greater length differences between homologous telomeres on chromosomes 9p, 15p and 15q were associated with breast cancer risk in pre-menopausal women, with aORs of 4.6 (2.3, 9.2), 3.1 (1.6, 6.0) and 2.8 (1.4, 5.4), respectively. When the subjects were categorized into quartiles, a dose-response relationship was observed for all of the above telomeres (P-for-trend ≤ 0.005). This study revealed that telomere deficiencies on chromosomes 9p, 15p, 15q and Xp were associated with breast cancer risk in pre-menopausal women. If confirmed in future studies, chromosomal arm-specific telomeres are likely to be a useful panel of blood-based biomarkers for breast cancer risk assessment, given their strong associations with breast cancer risk.
尽管端粒功能障碍是乳腺癌细胞的一个特征，但个体正常体细胞染色体端粒的缺陷与乳腺癌风险之间的关系尚未得到描述。进行了一项病例对照研究，以检测人类基因组中 92 个端粒的个体长度与 204 名新诊断的乳腺癌患者和 236 名健康对照者的乳腺癌风险之间的关系。通过端粒定量荧光原位杂交测量染色体臂特异性端粒长度。使用非条件逻辑回归估计风险关联。全基因组筛查发现，Xp 和 15p 染色体上较短的端粒长度与绝经前妇女的乳腺癌风险相关，调整后的优势比（aOR）分别为 2.5（95%置信区间= 1.3, 4.8）和 2.6（1.3, 5.0）。该研究还表明，9p、15p 和 15q 染色体上同源端粒之间的长度差异越大，与绝经前妇女的乳腺癌风险相关，aOR 分别为 4.6（2.3, 9.2）、3.1（1.6, 6.0）和 2.8（1.4, 5.4）。当将研究对象分为四组时，所有这些端粒都观察到剂量-反应关系（P-趋势≤0.005）。本研究表明，染色体 9p、15p、15q 和 Xp 上的端粒缺陷与绝经前妇女的乳腺癌风险相关。如果在未来的研究中得到证实，由于它们与乳腺癌风险的强烈关联，染色体臂特异性端粒很可能成为评估乳腺癌风险的有用血液生物标志物面板。
