Examining Stools for Colon Cancer Prevention: What Are We Really Looking for?
Colorado School of Public Health, Aurora, 80045, USA.Cancer Prevention Research (Impact Factor: 4.44). 10/2011; 4(10):1531-3. DOI: 10.1158/1940-6207.CAPR-11-0410
Fecal immunochemical testing (FIT) is superior to guiac-based testing if we are looking for blood in stools, as it has better one-time colorectal cancer sensitivity and specificity and better patient acceptance. In this issue of the journal, Cai and colleagues (beginning on page 1572) and Khalid-de Bakker and colleagues (beginning on page 1563) present new information about the one-time test performance of FIT. FIT will have a growing appeal to providers and health care systems as resources for clinical preventive services shrink and as incentives to expand colorectal screening rates increase, but there are good reasons to be cautious about the temptation to organize new FIT screening programs. Colorectal screening has two potential objectives: To find cancers in an earlier, more-treatable stage and to find and remove adenomas to prevent cancers from forming in the first place. Because most adenomas, even advanced adenomas, do not bleed, tests designed to identify occult blood in the stool are better for detecting colorectal cancer, whereas direct endoscopic visualization of the colorectum is better for prevention. Even if advanced adenomas did commonly bleed, low compliance with repeat annual testing will seriously erode the benefit of FIT.
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ABSTRACT: Colorectal cancer (CRC), the second most common cause of cancer-related mortality worldwide, is preventable with effective screening and removal of precursor lesions. Yet, screening efforts have been hampered by low participation rates and by performance limitations of the screening tools themselves. Stool DNA testing has emerged as a biologically rational and user-friendly strategy for the non-invasive detection of both CRC and critical precursor lesions. Unlike most conventional screening tools, stool DNA testing detects proximal and distal colorectal neoplasms equally well. Several key technical advances have led to increasingly accurate approaches for stool DNA testing including use of a DNA preservative buffer with stool collection, efficient target capture and amplification methods, broadly informative marker panels, and automated assay components. Based on recent studies, advanced multi-marker stool DNA tests including methylated markers, mutation markers and an assessment of faecal haemoglobin have been shown to detect CRC at sensitivities of 85% and higher and adenomas >1 cm at 60% and higher in a case-control environment. If the high accuracy of multi-marker stool tests is corroborated in multicentre screening studies on average-risk persons currently underway, then these stool tests could influence our CRC screening paradigm.This review discusses the biological basis, key technical advances, and recent clinical performance validation of stool DNA testing.
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ABSTRACT: Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3-5%) of cases arise from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well defined genes. In contrast, CRC is predominantly a late onset 'sporadic' disease, developing in individuals with no obvious hereditary syndrome. In recent years, genome wide association studies have discovered that over 40 genetic regions are associated with weak effects on sporadic CRC, and it has been estimated that increasingly large genome wide scans will identify many additional novel genetic regions. Subsequent experimental validations have identified the causally related variant(s) in a limited number of these genetic regions. Further biological insight could be obtained through ethnically diverse study populations, larger genetic sequencing studies and development of higher throughput functional experiments. Along with inherited variation, integration of the tumour genome may shed light on the carcinogenic processes in CRC. In addition to summarising the genetic architecture of CRC, this review discusses genetic factors that modify environmental predictors of CRC, as well as examples of how genetic insight has improved clinical surveillance, prevention and treatment strategies. In summary, substantial progress has been made in uncovering the genetic architecture of CRC, and continued research efforts are expected to identify additional genetic risk factors that further our biological understanding of this disease. Subsequently these new insights will lead to improved treatment and prevention of colorectal cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.