Grant Number:	1R01CA299916-01A1 Interpret this number
Primary Investigator:	Huang, Brian
Organization:	University Of Southern California
Project Title:	Synergistic Contribution of Lifestyle, Genetic and Epigenetic Factors to Colorectal Cancer Risk
Fiscal Year:	2026

ABSTRACT Colorectal cancer (CRC) is one of the most common cancers in the United States, with disproportionate burden across populations. As these differences are not fully explained by known lifestyle risk factors (e.g., smoking, BMI, physical activity), assessments of molecular factors or mechanisms are needed to further elucidate this population variation in CRC risk. Prior studies have investigated DNA methylation to identify epigenetic markers of CRC. However, most of these studies were conducted in homogenous populations using CRC tissue or post- diagnostic blood samples. Thus, there is limited information on epigenetic markers of CRC risk using pre- diagnostic, non-invasively collected blood samples, especially from a broad range of individuals with varying exposures and risk profiles. The objective of this study is to identify pre-diagnostic epigenetic biomarkers of CRC risk and to understand the epigenetic mechanisms of lifestyle and genetic CRC risk factors across multiple populations in the United States. In the discovery phase, we will conduct a nested case-control study of 1,500 CRC cases and 1,500 matched controls from the Multiethnic Cohort Study (MEC), a long-standing prospective cohort of >215,000 African American, Japanese American, Latino, Native Hawaiian, and White men and women. We will utilize existing resources from the MEC, including comprehensive epidemiologic questionnaire data, a large repository of pre-diagnostic biospecimens, and linkage with SEER registries and mortality databases. We will then validate our findings using data from the Atherosclerosis Risk in Communities (ARIC) Study, a large population-based cohort of African American and White individuals. Our specific aims are: 1) to identify pre-diagnostic epigenetic biomarkers for CRC risk across populations, 2) to identify epigenetic biomarkers for lifestyle and genetic risk factors for CRC, and 3) to develop a multiethnic integrative risk prediction model for CRC that incorporates lifestyle, genetic, and epigenetic factors. The findings from this study are expected to elucidate the underlying epigenetic determinants of CRC and enhance the prediction of CRC risk for multiple populations. This will be critical for improving strategies for targeted prevention and early detection and reducing the burden of CRC in the United States.





None