PREDICT

Colorectal cancer (CRC) is a major health concern worldwide. Its heterogeneous nature requires personalized prevention strategies to reduce the public health burden of the disease. The most promising agents for CRC chemoprevention are NSAIDs (e.g. aspirin, COX-2 inhibitors), which were associated with a significant reduction of adenoma recurrence in several trials (PreSAP, APACC, APPROVe), however, accompanied by increased risk of gastrointestinal and cardiovascular toxicities. We and others have shown that genetic variants can modify the risk of CRC in interacting with the mechanism of action of NSAIDs. In addition, our preliminary study suggests that certain variants interact with and modify the efficacy and symptoms/toxicity of NSAIDs in colorectal adenoma patients. The proposed study is a translational pharmacogenetic study ancillary to three multicenter trials on the secondary prevention of colorectal adenomas aimed to; establish the use of genetic variability as biomarkers for colorectal adenoma recurrence, and COX-2 inhibitor-related treatment efficacy, and symptoms/toxicity within the PreSAP; validate the identified biomarkers for the use of other COX inhibitors in samples from APPROVe (rofecoxib), as well as in samples from the APACC trial (aspirin), thus identifying similarities and differences in response to another COX-2 inhibitor. This project is a unique approach for developing personalized chemoprevention strategies by use of genetic fingerprints that can maximize the benefit/risk ratio of COX-2 inhibitors and aspirin in individuals at high risk of CRC.

Colorectal cancer (CRC) is a major health concern worldwide. Its heterogeneous nature requires personalized prevention strategies to reduce the public health burden of the disease. The most promising agents for CRC chemoprevention are NSAIDs (e.g. aspirin, COX-2 inhibitors), which were associated with a significant reduction of adenoma recurrence in several trials (PreSAP, APACC, APPROVe), however, accompanied by increased risk of gastrointestinal and cardiovascular toxicities. We and others have shown that genetic variants can modify the risk of CRC in interacting with the mechanism of action of NSAIDs. The PREDICT study was an ambitious project that was able to recruit DNA and clinical data from subjects participating in studies that were initiated and conducted 15-19 years ago. We aimed to develope personalized chemoprevention strategies by using genetic fingerprints that can maximize the benefit/risk ratio of COX-2 inhibitors and aspirin in individuals at high risk of CRC. With the vast majority of COX 2 inhibitors and NSAIDs usage for short and long run (cancer chemoprevention and rheumatic diseases) the study out come has important clinical implications. More than 1000 DNA samples were collected and genotype. Now we are trying to perform the bioinformatics as the German partner has not been able to perform. If more funding is avilable, from the budget that were not used in Germany, then it can, and should, be conducted by the coordinator.