Colorectal cancer is a biologically heterogeneous disease with somatic mutations in many driver genes such as APC, BRAF, P53 or PIK3CA, leading to multiple tumor subtypes. Large-scale sequencing efforts like The Cancer Genome Atlas (TCGA) fueled discovery of many driver genes, allowing for better definition of tumor subtypes that develop through activation of diverse neoplastic pathways. However, the relationship of etiologic risk factors for colorectal cancer such as germline genetic, lifestyle, and environmental risk factors with molecularly defined tumor subtypes have not been comprehensively studied. Additionally, there are few sizeable studies assessing tumor characteristics, germline genetics, and epidemiologic risk factors in relation to survival outcomes. To address this research gap, we harmonized existing tumor characteristics from over 12,000 colorectal cancer patients and are conducting targeted DNA sequencing on approximately 7,000 colorectal cancer patients. Investigating the associations of etiological and clinical risk factors with the molecular pathology of tumors will provide unique insight into carcinogenic mechanisms and offers the promise of improving public health by optimizing the biological basis for colorectal cancer prevention and prognosis.

Aside from somatic genetic drivers, the immune system plays a pivotal role in the initiation and progression of colorectal cancer. While the presence of a strong immune response has been consistently associated with better patient outcomes, little is known about the factors that specifically drive the immune response. Therefore, we are conducting studies to identify host and tumor factors (e.g., germline genetic, environmental, somatic mutations, and tumor microbiome) associated with immune response in colorectal cancer to improve our understanding of colorectal cancer immunity. This research provides an unprecedented opportunity to comprehensively investigate the epidemiology of immune response in colorectal cancer in a sizeable dataset. Insights gained through these novel studies could ultimately inform development of emerging immunotherapies and tailored immunoprevention strategies.

While an increasing number of tumor profiling studies are conducted in non-Hispanic White colorectal cancer patients and, to a smaller extent, in Asian patients, very little is known about the molecular changes and immune response across diverse racial and ethnic groups, including African American and Alaska Native people, who have substantially higher incidence and mortality rates than other populations. To address this gap, we developed the Translational Research Program in Colorectal Cancer Disparities.