Multitarget Stool DNA Testing for Colorectal-Cancer Screening
ABSTRACT 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.
- SourceAvailable from: Timothy Barrow
- "The benefit of using stool samples to identify colonic neoplasms has recently been demonstrated. Following promising results in the identification of neoplasms in patients with inflammatory bowel disease , methylation of BMP3 and NDRG4 were taken forward for use in conjunction with an immunochemical assay for haemoglobin and the detection of KRAS mutations, using bactin as a reference gene to establish DNA levels, for the detection of colorectal tumours . Using an algorithm to calculate a score based upon these measurements, this stool-based approach offered superior sensitivity to the faecal immunochemical test in the detection of tumours (92% vs 74%) and advanced precancerous lesions (42% vs 24%), at the expense of a reduction in specificity (87% vs 95%). "
Article: Epigenetic Epidemiology of Cancer.[Show abstract] [Hide abstract]
ABSTRACT: Epigenetic epidemiology includes the study of variation in epigenetic traits and the risk of disease in populations. Its application to the field of cancer has provided insight into how lifestyle and environmental factors influence the epigenome and how epigenetic events may be involved in carcinogenesis. Furthermore, it has the potential to bring benefit to patients through the identification of diagnostic markers that enable the early detection of disease and prognostic markers that can inform upon appropriate treatment strategies. However, there are a number of challenges associated with the conduct of such studies, and with the identification of biomarkers that can be applied to the clinical setting. In this review, we delineate the challenges faced in the design of epigenetic epidemiology studies in cancer, including the suitability of blood as a surrogate tissue and the capture of genome-wide DNA methylation. We describe how epigenetic epidemiology has brought insight into risk factors associated with lung, breast, colorectal and bladder cancer and review relevant research. We discuss recent findings on the identification of epigenetic diagnostic and prognostic biomarkers for these cancers.Biochemical and Biophysical Research Communications 08/2014; 455(1-2). DOI:10.1016/j.bbrc.2014.08.002 · 2.28 Impact Factor
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ABSTRACT: Colorectal-cancer screening in the United States is a success story. The American Cancer Society recently reported that rates of death from colorectal cancer are down by 46% from their peak.(1) There is good evidence that screening efforts have played an important role in the trend.(2) However, work remains to be done, since approximately one third of Americans report not being current with screening.(3) One approach to increase screening uptake is to broaden the available test options. On the basis of current U.S. Preventive Services Task Force guidelines, there are three recommended options: fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy. . . .New England Journal of Medicine 03/2014; 370(14). DOI:10.1056/NEJMe1400092 · 54.42 Impact Factor
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ABSTRACT: Worldwide, colorectal (CRC) is the third most common form of cancer, after lung and breast cancer, and the fourth most common cause of cancer death, although in developed countries CRC incidence is higher and it accounts for an even higher proportion of cancer deaths. Successful treatment of early-stage CRC confers substantial survival advantage, and there is now overwhelming evidence that screening average-risk individuals for CRC reduces the incidence and disease-specific mortality. In spite of considerable research for new biomarkers for CRC, the detection of blood in faeces remains the most effective screening tool. The best evidence to date for population-based CRC screening comes from randomised-controlled trials that used a guaiac-based faecal occult blood test (gFOBt) as the first-line screening modality, whereby test-positive individuals are referred for follow-up investigations, usually colonoscopy. A major innovation in the last ten years or so has been the development of other more analytically sensitive and specific screening techniques for blood in faeces. The faecal immunochemical test for haemoglobin (FIT) confers substantial benefits over gFOBt in terms of analytical sensitivity, specificity and practicality and FIT are now recommended for CRC screening by the European guidelines for quality assurance in colorectal cancer screening and diagnosis. The challenge internationally is to develop high quality CRC screening programmes for which uptake is high. This is especially important for developing countries witnessing an increase in the incidence of CRC as populations adopt more westernised lifestyles. This review describes the tests available for CRC screening and how they are being used worldwide. The reader will gain an understanding of developments in CRC screening and issues that arise in choosing the most appropriate screening test (or tests) for organised population-based screening internationally and optimising the performance of the chosen test (or tests). Whilst a wide range of literature has been cited, this is not a systematic review. The authors provide FOBT CRC screening for a population of 14.6 million in the south of England and the senior author (SPH) was the lead author of the European guidelines for quality assurance in colorectal cancer screening and diagnosis and leads the World Endoscopy Organization Colorectal Cancer Committee's Expert Working Group on 'FIT for Screening'.Clinical biochemistry 04/2014; 47. DOI:10.1016/j.clinbiochem.2014.04.019 · 2.28 Impact Factor