Advances in biophotonics detection of field carcinogenesis for colon cancer risk stratification

The process of neoplastic transformation of the colon involves a progression through hyperproliferative epithelium through the aberrant crypt foci→small adenoma→large adenoma→invasive cancer→metastatic disease. These are orchestrated by sequential genetic and epigenetic events which provide the underpinnings of cellular alterations such as early induction in proliferation/ suppression of apoptosis, along with the late stage increase in invasiveness. Colorectal cancer (CRC) averages 49-111 mutations per tumor encompassing 10-15 critical signaling pathways[1]. Accumulating such a high number of mutations requires a fertile mutational field, which is the hallmark of colon carcinogenesis. While genetic susceptibility to colorectal cancer is well-known, at least half of the risk is believed to be due to exogeneous factors (e.g., obesity, diet, exercise). Understanding these risk factors represents a promising mode of tailoring screening modality and intensity. However, previous attempts using these factors (i.e., NCI risk calculator) have only been modestly successful with an area under receiver operating characteristics (ROC) curve (AUC) of just 0.61. One of the most important concepts is that risk is the interaction between these genetic and environmental components and is driven by the variety of polymorphisms. Thus, predicting risk is difficult given the complexity. On the other hand, the colonic mucosa represents the end product of the complex interplay between these multiple factors. The power of field carcinogenesis is that it reflects this interplay between genetics and environment.