Long telomeres in peripheral blood leukocytes are associated with an increased risk of soft tissue sarcoma.
Long telomeres in peripheral blood leukocytes are associated with an increased risk of soft tissue sarcoma.
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DOI：
10.1002/cncr.27984
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发表时间：
2013-05-15
期刊：
影响因子：
6.2
通讯作者：
Gu, Jian
中科院分区：
文献类型：
--
作者：
Xie, Hui;Wu, Xifeng;Wang, Shui;Chang, David;Pollock, Raphael E.;Lev, Dina;Gu, Jian
由染色体末端的核苷酸序列TTAGGG的长串联重复序列组成的人类端粒对于维持染色体稳定性是必需的。先前的流行病学研究表明，外周血白细胞（PBL）中较短的端粒长度与许多癌症的发生有关。然而，PBL端粒长度和软组织肉瘤（STS）的风险之间的关系尚未研究。在本病例对照研究中，我们使用实时聚合酶链反应（PCR）测定PBL中的相对端粒长度（RTL）。研究参与者包括137名组织学确诊的STS（病例）患者，既往没有接受过化疗或放疗，以及137名与病例年龄、性别和种族频率匹配的健康对照。病例组的RTL显著长于对照组（1.46 ± 0.42vs.1.15 ± 0.39，P < 0.001）。以对照组的RTL中位数为界值，端粒长度较长的个体与端粒长度较短的个体相比，STS风险显著增加（校正比值比=4.71; 95%置信区间，2.63-8.44）。当参与者根据健康对照的三分位数或四分位数RTL值进一步分为三组或四组时，我们观察到较长的RTL和STS风险增加之间存在显着的剂量反应关系。本研究提供了第一个流行病学证据，即PBL中较长的端粒长度与STS风险增加显著相关，可能表明端粒维持在STS发展中的重要作用。
Human telomeres consisting of long, tandem repeats of the nucleotide sequence TTAGGG at the chromosome ends are essential for maintaining chromosomal stability. Previous epidemiologic studies have indicated that shorter telomere length in peripheral blood leukocytes (PBLs) is associated with the development of many cancers. However, the relationship between PBL telomere length and the risk of soft tissue sarcoma (STS) has not been investigated. We determined the relative telomere length (RTL) in PBLs using real-time polymerase chain reaction (PCR) in this case-control study. The study participants included 137 patients with histologically confirmed STS (cases) with no prior chemotherapy or radiotherapy and 137 healthy controls frequency-matched to cases on age, gender, and ethnicity. The cases had significantly longer RTL than controls did (1.46 ± 0.42 for cases vs.1.15 ± 0.39 for controls, P < 0.001). Using median RTL in the controls as a cutoff, individuals with long telomere length were associated with a significantly increased risk of STS compared with those with short telomere length (adjusted odds ratio =4.71; 95% confidence interval, 2.63–8.44). When participants were categorized further into three or four groups according to the tertile or quartile RTL values of healthy controls, we observed a significant dose-response relationship between longer RTL and increased risks of STS. The present study provides the first epidemiologic evidence that longer telomere length in PBLs is significantly associated with an increased risk of STS, potentially suggesting an important role for telomere maintenance in STS development.
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DOI：
10.1158/1055-9965.epi-08-0935
发表时间：
2009-03
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Kim S;Parks CG;DeRoo LA;Chen H;Taylor JA;Cawthon RM;Sandler DP
通讯作者：
Sandler DP
影响因子：
3.7
作者：
Ma H;Zhou Z;Wei S;Liu Z;Pooley KA;Dunning AM;Svenson U;Roos G;Hosgood HD 3rd;Shen M;Wei Q
通讯作者：
Wei Q
影响因子：
11.2
作者：
Pooley KA;Sandhu MS;Tyrer J;Shah M;Driver KE;Luben RN;Bingham SA;Ponder BA;Pharoah PD;Khaw KT;Easton DF;Dunning AM
通讯作者：
Dunning AM
影响因子：
6.6
作者：
Fernandez-Egea, Emilio;Bernardo, Miguel;Kirkpatrick, Brian
通讯作者：
Kirkpatrick, Brian
在前瞻性病例 - 霍特分析中，外周血和乳腺癌风险的端粒长度：姐妹研究的结果。
影响因子：
2.3
作者：
Kim, Sangmi;Sandler, Dale P.;Carswell, Gleta;De Roo, Lisa A.;Parks, Christine G.;Cawthon, Richard;Weinberg, Clarice R.;Taylor, Jack A.
通讯作者：
Taylor, Jack A.