多靶点粪便 DNA 检测用于结直肠癌筛查。
Multitarget stool DNA testing for colorectal-cancer screening.
机构信息
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.).
出版信息
N Engl J Med. 2014 Apr 3;370(14):1287-97. doi: 10.1056/NEJMoa1311194. Epub 2014 Mar 19.
BACKGROUND
An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening.
METHODS
We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings.
RESULTS
Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT.
CONCLUSIONS
In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.).
背景
一种准确、非侵入性的检测方法可以提高结直肠癌筛查的效果。
方法
我们比较了一种非侵入性、多靶点粪便 DNA 检测方法与粪便免疫化学检测（FIT）在结直肠癌平均风险人群中的应用。该 DNA 检测包括 KRAS 基因突变、异常 NDRG4 和 BMP3 甲基化以及 β-肌动蛋白的定量分子检测，以及血红蛋白免疫检测。结果采用逻辑回归算法生成，183 分或以上为阳性。缓冲液中每毫升血红蛋白含量超过 100ng 被认为是阳性。检测是在结肠镜检查结果之外进行的。
结果
在可评估的 9989 名参与者中，65 人（0.7%）患有结直肠癌，757 人（7.6%）在结肠镜检查中发现晚期癌前病变（高级腺瘤或直径大于等于 1cm 的无蒂锯齿状息肉）。DNA 检测对结直肠癌的敏感性为 92.3%，FIT 为 73.8%（P=0.002）。DNA 检测对高级癌前病变的敏感性为 42.4%，FIT 为 23.8%（P<0.001）。DNA 检测对高级别不典型增生息肉的检出率为 69.2%，FIT 为 46.2%（P=0.004）；直径大于等于 1cm 的锯齿状无蒂息肉的检出率分别为 42.4%和 5.1%（P<0.001）。在非高级或阴性发现的参与者中，DNA 检测和 FIT 的特异性分别为 86.6%和 94.9%（P<0.001），在结肠镜检查阴性的参与者中分别为 89.8%和 96.4%（P<0.001）。为了发现一个癌症，需要筛查的人数分别为 154 人进行结肠镜检查，166 人进行 DNA 检测，208 人进行 FIT 检测。
结论
在结直肠癌平均风险的无症状人群中，多靶点粪便 DNA 检测比 FIT 检测检测到的癌症明显更多，但假阳性结果更多。（由 Exact Sciences 资助；ClinicalTrials.gov 编号，NCT01397747）。
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