Disease Comorbidity Network Guides the Detection of Molecular Evidence for the Link Between Colorectal Cancer and Obesity

Epidemiological studies suggested that obesity increases the risk of colorectal cancer (CRC). The genetic connection between CRC and obesity is multifactorial and inconclusive. In this study, we hypothesize that the study of shared comorbid diseases between CRC and obesity can offer unique insights into common genetic basis of these two diseases. We constructed a comorbidity network based on mining health data for millions of patients. We developed a novel approach and extracted the diseases that play critical roles in connecting obesity and CRC in the comorbidity network. Our approach was able to prioritize metabolic syndrome and diabetes, which are known to be associated with obesity and CRC through insulin resistance pathways. Interestingly, we found that osteoporosis was highly associated with the connection between obesity and CRC. Through gene expression meta-analysis, we identified novel genes shared among CRC, obesity and osteoporosis. Literature evidences support that these genes may contribute in explaining the genetic overlaps between obesity and CRC.