Telomere deficiencies on chromosomes 9p, 15p, 15q and Xp: potential biomarkers for breast cancer risk.
Telomere deficiencies on chromosomes 9p, 15p, 15q and Xp: potential biomarkers for breast cancer risk.
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DOI：
10.1093/hmg/ddq461
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发表时间：
2011-01
影响因子：
3.5
通讯作者：
Yun-Ling Zheng;Xin Zhou;C. Loffredo;P. Shields;Bing Sun
中科院分区：
文献类型：
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作者：
Yun-Ling Zheng;Xin Zhou;C. Loffredo;P. Shields;Bing Sun
虽然端粒功能障碍是乳腺癌细胞的一个特征，但正常体细胞中单个染色体端粒缺陷与乳腺癌风险之间的关系尚未得到表征。在204名新诊断的乳腺癌患者和236名健康对照中进行了一项病例对照研究，以检查人类基因组中92个端粒的个体长度与乳腺癌风险之间的关联。染色体臂特异性端粒长度测量端粒定量荧光原位杂交。非条件Logistic回归用于估计风险相关性。这项全基因组筛查发现，染色体Xp和15 p上较短的端粒长度与绝经前妇女患乳腺癌的风险相关，调整后的比值比（aOR）分别为2.5（95%CI = 1.3，4.8）和2.6（1.3，5.0）。该研究还显示，染色体9 p，15 p和15 q上同源端粒之间的较大长度差异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）。当受试者被分类为四分位数时，观察到所有上述端粒的剂量-反应关系（趋势P ≤ 0.005）。这项研究表明，染色体9 p，15 p，15 q和Xp上的端粒缺陷与绝经前妇女患乳腺癌的风险有关。如果在未来的研究中得到证实，染色体臂特异性端粒很可能成为乳腺癌风险评估的一组有用的血液生物标志物，因为它们与乳腺癌风险密切相关。
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.