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外周血端粒较短与进展期结直肠腺瘤患者相关,可能成为一种潜在的生物标志物。

Shorter peripheral blood telomeres are a potential biomarker for patients with advanced colorectal adenomas.

机构信息

Medical Genetics, Mayo Clinic, Jacksonville, Florida, USA.

出版信息

Int J Biol Markers. 2012 Dec 27;27(4):e375-80. doi: 10.5301/JBM.2012.9347.

Abstract

BACKGROUND

Colorectal cancer (CRC) can be prevented by the early detection and removal of advanced adenomas (AAs) by colonoscopy. Our aim was to evaluate peripheral blood leukocyte (PBL) telomere length as a potential biomarker for the presence of AAs.

METHODS

PBL telomere length was measured in patients with AAs (n=35), in a control group of similarly aged patients who had a normal colonoscopy (n=145) and in a separate population group with no history of cancer, again similarly aged (n=495). Telomere measurements were performed using a quantitative PCR assay and reported as ratios of telomere and single copy gene measurements.

RESULTS

Telomere lengths tended to be lower in patients with AAs than in patients in the normal colonoscopy group (p<0.001) as well as those in the population group (p=0.011). A telomere/single copy gene ratio of 0.5 was found to have an estimated 94% sensitivity and a 56% specificity for AAs; a combination of sensitivity and specificity for which a value of >0.5 would reduce the odds of a patient having AAs by a factor of 0.11 (the negative likelihood ratio). Thirty three percent of individuals in the population group tested above this cutoff and could be considered at low risk for AAs.

CONCLUSIONS

PBL telomeres are shortened in patients with colorectal neoplasia, suggesting that PBL telomere length could be a promising non-invasive blood biomarker to pre-screen for risk of AAs prior to colonoscopy.

摘要

背景

通过结肠镜检查早期发现和切除高级腺瘤(AAs)可以预防结直肠癌(CRC)。我们的目的是评估外周血白细胞(PBL)端粒长度作为存在 AAs 的潜在生物标志物。

方法

在患有 AAs 的患者(n=35)、年龄相似且结肠镜检查正常的对照组患者(n=145)和无癌症史且年龄相似的单独人群组患者(n=495)中测量 PBL 端粒长度。使用定量 PCR 测定法进行端粒测量,并报告为端粒和单拷贝基因测量的比值。

结果

与正常结肠镜组患者(p<0.001)和人群组患者(p=0.011)相比,患有 AAs 的患者的端粒长度往往较低。端粒/单拷贝基因比值为 0.5 时,对 AAs 的估计灵敏度为 94%,特异性为 56%;对于灵敏度和特异性的组合,>0.5 的值将使患者发生 AAs 的几率降低 0.11 倍(负似然比)。人群组中有 33%的个体测试值高于此截止值,可以认为其发生 AAs 的风险较低。

结论

结直肠肿瘤患者的 PBL 端粒缩短,这表明 PBL 端粒长度可能是一种有前途的非侵入性血液生物标志物,可在结肠镜检查前对 AAs 的风险进行预筛查。

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