Department of Pediatrics, Stanford, CA, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):605-13. doi: 10.1158/1055-9965.EPI-09-0896.
Telomeres cap the ends of chromosomes and are composed of a series of noncoding hexamer repeats. Telomeres protect the integrity of DNA coding sequences and are integral to the maintenance of genomic stability. Previous studies have shown an association between shortened lymphocyte telomeres and increased risk for specific cancers. However, the association between telomere length and breast cancer risk is less clear. We examined the relative telomere length (RTL) in blood from women with no personal or family history of cancer (controls) compared with different populations of women with breast cancer and women at high genetic risk for developing breast cancer. RTL was determined as the telomere to single gene copy number ratio assessed by quantitative PCR. Breast cancer cases (low risk, n = 40; high risk, n = 62) had significantly longer RTL compared with unaffected controls (n = 50; mean RTL = 1.11 versus 0.84; P < 0.0001). The assessment of risk by RTL quartile showed an increased risk for breast cancer with each longer quartile, with the most significant risk observed in the longest quartile (odds ratio, 23.3; confidence interval, 4.4-122.3; P < 0.0003). Women without breast cancer but at high risk due to family history (n = 30) also showed longer telomeres than controls (mean RTL = 1.09 versus 0.84; P < 0.0001). Our analysis supports previous findings of longer RTL in breast cancer cases compared with controls, and is the first to observe longer RTL in women without breast cancer identified as high risk based on family history.
端粒位于染色体的末端，由一系列非编码六聚体重复序列组成。端粒保护 DNA 编码序列的完整性，是维持基因组稳定性的关键。先前的研究表明，淋巴细胞端粒缩短与某些癌症的风险增加有关。然而，端粒长度与乳腺癌风险之间的关联尚不明确。我们比较了无癌症个人或家族史的女性（对照组）与不同乳腺癌人群以及乳腺癌高危遗传女性的血液中端粒相对长度（RTL）。RTL 通过定量 PCR 评估的端粒与单基因拷贝数比来确定。乳腺癌病例（低危，n=40；高危，n=62）的 RTL 明显长于未受影响的对照组（n=50；平均 RTL=1.11 对 0.84；P<0.0001）。按 RTL 四分位数评估风险显示，随着 RTL 更长，乳腺癌的风险增加，最长四分位数观察到的风险最大（比值比，23.3；95%置信区间，4.4-122.3；P<0.0003）。无乳腺癌但因家族史而处于高危状态的女性（n=30）的端粒也比对照组长（平均 RTL=1.09 对 0.84；P<0.0001）。我们的分析支持先前发现的乳腺癌病例的 RTL 比对照组长，并且是第一个观察到基于家族史确定为高危的无乳腺癌女性 RTL 更长的研究。
