PD-011 Inexpensive biomarkers for determining individuals at increased risk for colorectal cancer and hence have the repeat screening colonoscopy after the first normal earlier than guidelines recommend

Abstract

Introduction: Screening for colorectal cancer (CRC) is currently based on colonoscopy and other methods such as the fecal occult blood test. We are interested in the role of blood-based genetic markers in CRC screening because of their low cost and relative nonintrusiveness. However, the performance of test strategies involving different numbers of markers of various properties needs further study.Methods: We have shown an association between colorectal cancer (185 cases vs. 93 controls) and SNP or deletion status for TGFBR1, GSTT1, INSR, telRNA, LRRC1, GSTM1, CHR8 and FOXO1. The information from all these tests was combined using a discriminant function. All information for each subject was condensed into a single index which gives the best discrimination between cases and controls. The index could be used to distinguish high-risk subjects from low-risk ones, so that the high-risk group would become the focus of further screening and early detection of cancer. Furthermore, various thresholds of the index could be defined to optimise the economic performance of the test for various relative costs of false positives or false negatives.Results: We have used data on the SNPs and deletions to enable us to evaluate the performance of the test based on different numbers of variants. The addition of variants led to increased sensitivity and specificity of the test. For example, with all eight markers the sensitivity was found to be 74.6% and the specificity 77.4%. With only three variants (TGFBR1, GSTT1 and INSR), sensitivity was 70.3% and specificity 67.7%.Conclusion: Presently the yield of mass screening for colorectal cancer has by its nature a vast number of persons of which the majority will not have cancer. Based on this fact, repeat screening after normal first colonoscopy has a low yield and still misses a certain number of intermediary cancers. By being able to predict a higher risk group, the repeat colonoscopy might have to be done earlier than stated by guidelines for these individuals. Although the cost of test with a panel of biomarkers depends on the number of markers and the particular ones chosen, a first estimate would be in the range $50 to $100 per individual, much less than the cost of a colonoscopy. Furthermore, the test could be carried out at any age, including much earlier than is recommended for colonoscopy. Introduction: Screening for colorectal cancer (CRC) is currently based on colonoscopy and other methods such as the fecal occult blood test. We are interested in the role of blood-based genetic markers in CRC screening because of their low cost and relative nonintrusiveness. However, the performance of test strategies involving different numbers of markers of various properties needs further study. Methods: We have shown an association between colorectal cancer (185 cases vs. 93 controls) and SNP or deletion status for TGFBR1, GSTT1, INSR, telRNA, LRRC1, GSTM1, CHR8 and FOXO1. The information from all these tests was combined using a discriminant function. All information for each subject was condensed into a single index which gives the best discrimination between cases and controls. The index could be used to distinguish high-risk subjects from low-risk ones, so that the high-risk group would become the focus of further screening and early detection of cancer. Furthermore, various thresholds of the index could be defined to optimise the economic performance of the test for various relative costs of false positives or false negatives. Results: We have used data on the SNPs and deletions to enable us to evaluate the performance of the test based on different numbers of variants. The addition of variants led to increased sensitivity and specificity of the test. For example, with all eight markers the sensitivity was found to be 74.6% and the specificity 77.4%. With only three variants (TGFBR1, GSTT1 and INSR), sensitivity was 70.3% and specificity 67.7%. Conclusion: Presently the yield of mass screening for colorectal cancer has by its nature a vast number of persons of which the majority will not have cancer. Based on this fact, repeat screening after normal first colonoscopy has a low yield and still misses a certain number of intermediary cancers. By being able to predict a higher risk group, the repeat colonoscopy might have to be done earlier than stated by guidelines for these individuals. Although the cost of test with a panel of biomarkers depends on the number of markers and the particular ones chosen, a first estimate would be in the range $50 to $100 per individual, much less than the cost of a colonoscopy. Furthermore, the test could be carried out at any age, including much earlier than is recommended for colonoscopy.