Channing Colorectal Cancer Research

A Multidisciplinary Approach to Understanding Colorectal Cancer Etiology, Heterogeneity, and Pathobiology to Improve Diagnosis, Prognosis, and Strategies for Prevention and Treatment

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in women and the third in men worldwide. It accounts for about 10% of total cancers and is the third-leading cause of cancer death in women and the fourth in men globally.

CRC is a multifactorial disease. The rates vary more than 10 times across the world, suggesting it is a largely preventable cancer. Screening also has a major impact on CRC.

Current Research

Investigators at the Channing Division of Network Medicine (CDNM) have built a comprehensive research strategy to:

• Study the epidemiology and progression of CRC
• Identify the genetic determinants of CRC
• Define key pathobiological mechanisms, influencing CRC susceptibility and tumor heterogeneity

We apply a multidisciplinary approach to understand CRC etiology, heterogeneity, and pathobiology to improve diagnosis and prognosis, and to develop primary and secondary strategies for prevention and therapeutics for treatment.

Achievements

Early research at Channing demonstrated that red and processed meat, alcohol, smoking, and obesity were associated with an increased risk of CRC, whereas folate, calcium, vitamin D, aspirin, and physical activity were associated with decreased risk of CRC. Moreover, modifiable factors, such as physical activity, vitamin D, folate, insulin and insulin-like growth factor binding protein-1, and diet quality, were identified to be associated with survival among CRC patients.

In recent years, molecular pathological epidemiological studies have been actively conducted and have shown refined results by molecular subtypes of CRC.

Genetics

Genetics is a crucial aspect of our research, including:

• Identifying CRC susceptibility loci using genome-wide association studies (GWAS) and whole genome sequencing
• Integrative analysis of multiple “omics” datasets, including gene expression and whole-exome sequencing of tumor tissue

Network approaches

CDNM scientists model molecular interactions using complex network approaches, for example:

• Addressing complex disease heterogeneity by building CRC phenotypic networks
• Identifying CRC molecular subtypes using networks
• Genetic drivers of immune recognition and evasion in CRC
• Whole-exome sequencing
• Metabolomics
• Microbiome

Study populations

Study populations developed by CDNM investigators include:

• Nurses’ Health Study
• Nurses’ Health Study II
• Health Professionals Follow-Up Study
• The Physicians’ Health Study

National and international collaborations

CDNM leads collaborations within such groups as the Colorectal Transdisciplinary Study, the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), An International Pooling Project of 17 Cohorts (plasma data), and the Pooling Project of Prospective Studies of Diet and Cancer.