Multitarget Stool DNA Testing for Colorectal-Cancer Screening
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 -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. ResultsOf 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.) A stool test that measures mutant KRAS, abnormal gene methylation, and hemoglobin detected significantly more colorectal cancers than a commercial fecal immunochemical test (FIT) but had more false positive results. Colorectal cancer is a major cause of death and disease among men and women in the United States.(1) The underlying neoplastic processes of colorectal carcinogenesis lend themselves to screening.(2) Evidence supports and guidelines endorse several tests and strategies,(3)-(5) and screening for colorectal cancer has been found to be cost-effective.(5)-(7) Despite the supporting evidence, recommendations, and availability of several screening tests, a substantial proportion of the U.S. population is not up to date with screening.(8) A simple, noninvasive test with high sensitivity for both colorectal cancer and advanced precancerous lesions might increase uptake and adherence rates, which could improve ...
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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: Epithelial cancer of the colon and rectum, also known as colorectal cancer (CRC), results from a progressive accumulation of genetic and epigenetic alterations that lead to uncontrolled growth of colonocytes, the cells lining the colon and rectum. CRC is the second leading cause of cancer-related deaths and the third most common cancer in men and in women in the U.S. Of all the patients diagnosed with CRC every year, it is estimated that the vast majority of CRCs are non-hereditary "sporadic cancers" with no apparent evidence of an inherited component. Sporadic CRC results from the cumulative effects of multiple genetic and epigenetic alterations caused by somatic mutations, which may themselves be the indirect result of several environmental factors. This review examines our current understanding of the major genetic alterations leading to colon cancer, options for prevention and early detection of CRC, and the currently available treatment approaches that may target these different genetic alterations.
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ABSTRACT: Colorectal cancer (CRC) is an important cause of mortality and morbidity in North America. Screening using a fecal occult blood test, flexible sigmoidoscopy, or colonoscopy reduces CRC mortality through the detection and treatment of precancerous polyps and early stage CRC. Although CRC screening participation has increased in recent years, large inequities still exist. Minorities, new immigrants, and those with lower levels of education or income are much less likely to be screened. This review provides an overview of the commonly used tests for CRC screening, disparities in CRC screening, and promising methods at the individual, provider, and system levels to reduce these disparities. Overall, to achieve high CRC participation rates and reduce the burden of CRC in the population, a multi-faceted approach that uses strategies at all levels to reduce CRC screening disparities is urgently required.Journal of Carcinogenesis 01/2014; 13:12. DOI:10.4103/1477-3163.144576