Application of Systems Genetics to Investigate Molecular Pathology of Early-Onset Colorectal Cancer

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the United States. The incidence of early-onset CRC (EOCRC) has been rising in the past few decades. Given the multifaceted nature of EOCRC, the genetic and environmental factors contributing to this malignancy have remained elusive. Systems genetics is a multi-omics tool that analyzes multiple genes as a collective network. Transcriptional correlation, protein-protein interaction network, functional annotation, and drug-gene interaction analyzes enable investigators to explore the functional roles of target genes and aid with discovery of novel diagnostic biomarkers and potential therapeutics. To clarify the objective of this work, this manuscript serves three purposes: a narrative review of recent systems genetics applications in EOCRC research, a step-by-step protocol for conducting these analyses, and a discussion of current advances in systems genetics to address limitations in generalizability and context dependence. Through this manuscript, we envision a future in which emerging oncology researchers adopt these tools into their investigations of EOCRC and other malignancies.