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粪便多靶点DNA检测在结直肠癌筛查中的应用
Multitarget Stool DNA Testing for Colorectal-Cancer Screening


Thomas F. Imperiale ... 肿瘤 其他 • 2014.04.03
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• 粪便潜血试验阳性而拒绝结肠镜检查的患者接受替代检查的情况 • 使用粪便免疫化学测试进行6轮结直肠癌筛查 • 血红蛋白浓度与结直肠肿瘤的风险相关,即使在FIT阴性人群中 • 更新版结直肠癌筛查建议

中国粪便基因筛查大肠癌的时代来临了吗?

 

陈功

广州中山大学肿瘤防治中心结直肠科,广州东风东路651号,510060

 

大肠癌的筛查,是被WHO(世界卫生组织)最早认定的能通过筛查手段来有效降低健康人群中大肠癌发病率和死亡率的癌症筛查之一;筛查带来的获益目前已经在美国肠癌流行病学中清晰地体现出来——美国是唯一一个结直肠癌发病率和死亡率均呈下降趋势的西方发达国家,其中筛查居功至伟。

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摘要


背景

一种精确而无创的检查有可能提高结直肠癌筛查的有效性。

 

方法

在结直肠癌发病风险处于平均水平的人群中,我们对无创粪便多靶点DNA检测与粪便免疫化学检测(FIT)进行了比较。粪便DNA检测项目包括KRAS突变、NDRG4异常、BMP3甲基化、β-actin基因的定量检测加血红蛋白免疫检测。通过逻辑斯蒂回归分析计算出结果,结果≥183则被认为阳性。对于FIT,血红蛋白≥100 ng/mL缓冲液则被认为阳性。结肠镜检查结果不会对这两种检测过程产生影响。

 

结果

在9,989位可以评估的参与者中,65例(0.7%)经结肠镜检查被诊断为结直肠癌,757例(7.6%)被诊断为高级别癌前病变(高级别腺瘤或最大直径≥1 cm的广基锯齿状息肉)。DNA检测和FIT检出结直肠癌的敏感性分别为92.3%和73.8%(P=0.002),而检出高级别癌前病变的敏感性分别为42.4%和23.8%(P<0.001)。对于高级别不典型增生息肉的检出率,DNA检测法为69.2%,而FIT法则为46.2%(P=0.004);而对于最大直径≥1 cm广基锯齿状息肉的检出率,DNA检测法与FIT法分别为42.4%和5.1%(P<0.001)。在结肠镜诊断为非高级别病变或阴性的参与者中,DNA检测和FIT的特异性分别为86.6%和94.9%(P<0.001)。结肠镜结果阴性的参与者中,两者的特异性分别为89.8%和96.4%(P<0.001)。要检出1例结直肠癌患者,结肠镜需要筛查154人,DNA检测需要筛查166人,FIT需要筛查208人。

 

结论

在结直肠癌发病风险处于平均水平并且没有症状的的人群中,与FIT相比,粪便多靶点DNA检测检出了显著更多的结直肠癌患者,但是假阳性率也较高。(本项研究由Exact Scineces赞助;ClinicalTrials.gov注册号为NCT01397747)。





作者信息

Thomas F. Imperiale, M.D., David F. Ransohoff, M.D., Steven H. Itzkowitz, M.D., Theodore R. Levin, M.D., Philip Lavin, Ph.D., Graham P. Lidgard, Ph.D., David A. Ahlquist, M.D., and Barry M. Berger, M.D.
From the Department of Medicine, Indiana University School of Medicine, the Regenstrief Institute, the Simon Cancer Center, and the Center for Innovation at Roudebush Veterans Affairs Medical Center — all in Indianapolis (T.F.I.); the Departments of Medicine and Epidemiology and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (D.F.R.); the Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York (S.H.I.); Kaiser Permanente Medical Center, Walnut Creek, CA (T.R.L.); Boston Biostatistics Research Foundation, Framingham MA (P.L.); Exact Sciences, Madison, WI (G.P.L., B.M.B.); and the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN (D.A.A.). Address reprint requests to Dr. Imperiale at Indiana University Medical Center–Regenstrief Institute, 1050 Wishard Blvd., Indianapolis, IN 46202.

 

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