Grant Details
Grant Number: |
1R50CA274122-01A1 Interpret this number |
Primary Investigator: |
Ugai, Tomotaka |
Organization: |
Brigham And Women'S Hospital |
Project Title: |
Integration of Immunology and Microbiology Into Molecular Pathological Epidemiology of Colorectal Cancer |
Fiscal Year: |
2023 |
Abstract
Summary
Colorectal cancer is a heterogenous disease influenced by somatic mutations, microbiota, host immunity,
and risk factor exposures, necessitating integrative research approaches to better understand the etiology.
The proposed project plans to integrates immunology and microbiology into molecular pathological
epidemiology (MPE) to gain insights into the interactive role of exposures, microbiota, immune cells, and
tumor cells in colorectal cancer and adenoma. This project also plans to develop novel statistical and
computational methods for such research. This project leverages tumor tissue datasets in various
populations, including the Nurses' Health Study (NHS), NHS2, Health Professionals Follow-up Study,
Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Multiethnic Cohort Study (MEC),
Partners Colonoscopy Cohort (PCC), and CALGB/SWOG 80702 trials. Our multi-level databases have
accumulated information on long-term lifestyle factors and tumoral features of colorectal cancer (CRC) and
adenoma. Our research involves the assessment of various immune cells and microbiota in tumor tissue
using multispectral assays combined with digital image analyses and machine learning algorithms.
Characteristics of molecular pathology, microorganisms, and immunity in tumor tissue will shed light on the
carcinogenic process. Diet and lifestyle factors will be assessed in relation to incidence of CRC (or
adenoma) subtyped by microbial and/or immune features, and in relation to clinical outcomes of these tumor
subtypes. The MPE approach is expected to reveal currently unknown risk and prognostic factors for CRC
and early-onset CRC, the incidence of which has increased globally for uncertain reasons. Moreover,
examining effects of modifiable lifestyle factors on immune cells and microorganisms in tumor tissue will
open new ways to develop personalized preventive strategies. Efforts will be made to replicate findings
using other independent datasets whenever possible. New statistical methods will address analytical issues
such as continuous subtyping, missing biomarker data, intratumor spatial variations, high-dimensional tumor
data, mediation analyses, and prediction models. Furthermore, novel computational algorithms will be
developed to decipher the spatial patterns of immune cell subsets and tumor cells in the tumor
microenvironment. Integrative epidemiological analyses of immunology and microbiology will generate
provide the scientific foundation for exploring roles of anti-tumor immunity and microbiota in CRC
development. In addition, this project will advance population cancer sciences via the development of new
statistical and computational methods.
Publications
None