Mining cancer-specific disease comorbidities from a large observational health database

Cancer comorbidities often reflect the complex pathogenesis of cancers and provide valuable clues to discover the underlying genetic mechanisms of cancers. In this study, we systematically mine and analyze cancer-specific comorbidity from the FDA Adverse Event Reporting System. We stratified 3,354,043 patients based on age and gender, and developed a network-based approach to extract comorbidity patterns from each patient group. We compared the comorbidity patterns among different patient groups and investigated the effect of age and gender on cancer comorbidity patterns. The results demonstrated that the comorbidity relationships between cancers and non-cancer diseases largely depend on age and gender. A few exceptions are depression, anxiety, and metabolic syndrome, whose comorbidity relationships with cancers are relatively stable among all patients. Literature evidences demonstrate that these stable cancer comorbidities reflect the pathogenesis of cancers. We applied our comorbidity mining approach on colorectal cancer and detected its comorbid associations with metabolic syndrome components, diabetes, and osteoporosis. Our results not only confirmed known cancer comorbidities but also generated novel hypotheses, which can illuminate the common pathophysiology between cancers and their co-occurring diseases.