Integrated Molecular Epidemiology of Colorectal Cancer

Background: Colorectal cancer (CRC) is a heterogeneous disease, arising from a complex environment of host inflammation and gut microbes. We investigated whether the novel circulating inflammatory molecule, Macrophage Inhibitory Cytokine-1 (MIC-1), was associated with risk of CRC and CRC-associated mortality. In addition, to gain insights into the role of the gut microbiome in CRC development, we explored how a particular microbial species, Fusobacterium nucleatum, may mediate the association between diet and CRC incidence. Finally, to evaluate the fecal microbiome as a biomarker for CRC, we measured the temporal dynamics and stability of gut microbiome communities, metagenomes, and metatranscriptomes in a large prospective cohort. Methods: Data for these prospective analyses were collected from two ongoing cohorts, the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). In both cohorts, participants have returned questionnaires every 2 years to provide information about lifestyle and dietary factors, medication use, and diagnoses of CRC and other diseases. We measured plasma MIC-1 in pre-diagnostic blood samples (1990 in the NHS; 1994 in the HPFS) drawn