WP2: Epidemiological correlates of the colorectal cancer microbiome
Colorectal cancer (CRC) most often occurs sporadically (as compared to genetic forms of the disease) and is one of the leading causes of cancer-related death worldwide. Environmental factors contribute substantially to CRC risk and development, particularly the intestinal microbiota. The project overall aims to understand the role of aetiologic factors in tumor development with epidemiologic features in relation to the tumor tissue microbiome. Our work package hypothesis is that Lifestyle risks, environmental exposures, diet, and cancer phenotypes are each associated with features of the colorectal cancer microbiome.
Recently, newer cancer treatments have begun to utilize the tools inherent in our immune system to better treat and control the disease. The immune system plays critical roles in the body’s response to CRC. However, it remains uncertain how this relationship between CRC and immunity differs between various bacteria. The enhancement of the activity of the immune system via changes in various lifestyle behaviors is of great interest.
Unlike genetic factors, both the microbiome and diet are modifiable and represent broadly actionable targets for CRC prevention and therapy. However, neither the causal molecular mechanisms nor corresponding microbes have been pinpointed for CRC. We thus propose to identify metabolic and genetic factors within CRC-associated microbes and their molecular regulatory consequences in the gut. We will perform the first analysis of CRC-associated microbial genetics in the largest collection of human gut microbiomes created to date, spanning over ten different study populations. We will further assess transcriptional regulatory consequences of these microbial genetic variants and their interaction with dietary and lifestyle factors that contribute to CRC.
Work Package Leaders
Curtis Huttenhower, PhD
Co-Investigator, Harvard TH Chan School of Public Health
Professor of Computational Biology and Bioinformatics
Departments of Biostatistics and Immunology and Infectious Diseases
Associate Member, Broad Institute of MIT and Harvard
Co-director, Harvard Chan Microbiome in Public Health Center
Shuji Ogino, MD, PhD, MS
Co-Investigator, JBrigham and Women’s Hospital, Harvard T.H. Chan School of Public Health/ Harvard Medical School Broad Institute of MIT and Harvard
- Professor of Pathology, Brigham & Women’s Hospital, Harvard Medical School
- Professor (Epidemiology), Harvard T.H. Chan School of Public Health
- Chief Program in Molecular Pathological Epidemiology, Brigham and Women’s
- Associate Member, Broad Institute of MIT and Harvard
Lee Jones, MBA
Lee was diagnosed with Stage IV colon cancer in March 2004, and since undergoing several rounds of chemotherapy and a liver resection in July 2006 has been cancer free. Lee has a BA in Psychology and an MBA in Finance and had a successful executive career in government, banking, consulting, and not-for-profit organizations.