Over the past 20 to 30 years, considerable progress has been made in our understanding of colorectal carcinogenesis. Multistep genetic and histological tumor initiation, promotion, and progression accounts for the established adenoma to carcinoma sequence for the majority of CRCs. However, until we gain a better understanding of the entire cancer process, primary CRC prevention will remain an elusive goal. On the other hand, secondary CRC prevention can now be obtained through screening with routine technologies such as FOBT, FS, DCBE, and standard colonoscopy. Notwithstanding universal endorsement for CRC screening, less than 50% of individuals at average risk have undergone a screening examination of any type - a fact that is particularly worrisome since polypectomy can prevent invasive CRC. Indeed, the long-term multistep adenoma to carcinoma sequence provides not only the biologic rationale and opportunity, but even the obligation and responsibility for early colorectal detection. Yet, the benefit of CRC screening is not fully realized in the United States. Future research should elucidate the barriers to routine screening recommendations, determine the preferred screening method, and promote the development of promising new technologies. It will be important to assess issues related to acceptance and compliance with guidelines, as well as test availability, performance characteristics, reproducibility, and safety for individuals at average risk and high risk for developing CRC. Indeed, all tests may not be appropriate for all individuals. For many valid reasons, it may not be necessary or even practical to screen all averagerisk individuals with the current gold standard (screening colonoscopy). A tiered or layered approach might be more appropriate with lower risk individuals receiving the least intensive and least invasive procedures and higher risk individuals having the more intensive procedures. Proper risk stratification would not only spare lower risk individuals from unnecessary procedures but would also save valuable resources for higher risk individuals. However, proper risk stratification will require a more complete knowledge of the many gene-gene and gene-environmental causes of CRC. Large-scale randomized clinical trials with cancer-specific endpoints would provide the most definitive evidence for determining the preferred screening procedure by risk assessment. However, efficacy in a controlled clinical environment might not result in effectiveness in the general population. Moreover, in the context of limited financial resources and emerging technologies, these large-scale clinical trials may not be affordable or practical.212 Future research may rely heavily on smaller studies, built on the successes of the past. However, determining the appropriate screening test for all individuals is a worthy goal, given the feasibility and impact for completely eliminating the risk of CRC in the general population.
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