Molecular pathological epidemiology of colorectal cancer

Principal Investigator

Name
Ulrike Peters

Degrees
Ph.D, M.P.H

Institution
Fred Hutchinson Cancer Center

Position Title
Associate Director, Public Health Sciences

Email
upeters@fredhutch.org

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
PLCO-98

Initial CDAS Request Approval
Jul 22, 2014

Title
Molecular pathological epidemiology of colorectal cancer

Summary
Colorectal cancer (CRC), the second most commonly diagnosed cancer, is a biologically heterogeneous disease. Molecular characterization of tumors has provided evidence of multiple tumor subtypes that develop through activation of diverse neoplastic pathways. Next-generation sequencing has identified mutated genes in colorectal tumors, and has allowed better definition of tumor subtypes by mutated genes and pathways. We propose investigating the relationship between etiologic factors for CRC—such as germline genetic, lifestyle, and environmental risk factors— and tumor subtype to help improve understanding of the underlying carcinogenic mechanisms that result in different molecular subtypes of CRC. We propose utilizing PLCO germline GWAS and sequence data (EEMS Proposals 2006-00285 and 2009-00554), tumor sequence data, treatment data, and outcome data in conjunction with data from additional studies from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) for this project.

Aims

This project aims to utilize the data from PLCO, in conjunction with the data from GECCO, to investigate associations between commonly defined CRC subtypes and common and rare germline genetic variants across the genome, and as well as lifestyle, environmental, and familial risk factors. Additionally, we will utilize tumor sequence data to investigate the associations between CRC subtypes defined by mutated pathways and common and rare germline genetic variants across the genome, and as well as lifestyle, environmental, and familial risk factors. Finally, we will complete exploratory analyses of the relationships between etiologic factors for CRC (i.e. germline genetic, lifestyle, and environmental risk factors), tumor subtypes (as identified by mutated pathways and tumor characteristics), treatment, and outcome.