# Dietary Carcinogens for Colorectal Cancer

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $358,680

## Abstract

Project Summary
Colorectal cancer is the second leading cause of cancer-related death in the United States. About one third of
colorectal cancer deaths are attributable to inherited factors, yet high-penetrance, germline variants that
increase colorectal cancer risk more than 3-fold (like APC) only account for ~5% of all cases. The vast
majority of colorectal cancers involve the interaction of genes with the environment, particularly in
instances involving common low-penetrance variants. Extensive investigation into low-penetrance,
multifactorial predisposition to colorectal cancer is now beginning to bear fruit, with important implications for
understanding disease pathogenesis and developing new diagnostic, preventive, and therapeutic strategies.
However, the role of environmental exposure such as dietary carcinogens in colorectal cancer and its
interaction with genetic susceptibility alleles are not well understood. Epidemiological estimates suggest that
~70% of colorectal cancers are attributable to carcinogens via ingestion. Benzo[a]pyrene (BaP), a ubiquitous
environmental hydrocarbon found in burnt foods and drinking water, has been associated with increased risk of
colorectal cancer. A novel noncoding genetic variant located in the polyadenylation signal of the p53 gene was
recently identified as a low-penetrance genetic risk variant in colorectal cancer. This p53 variant is positioned
uniquely among colorectal cancer-susceptibility alleles in that it is noncoding and present at higher frequency.
About 1 in 50 in general populations, i.e., over 6 million Americans and 100 million people worldwide, carry this
mutant. We have compelling preliminary data establishing a link between exposure to BaP and increased
colorectal cancer incidence associated with the p53 polyadenylation signal variant. Based on this evidence,
we hypothesize that the interaction of environmental BaP and low-penetrance susceptibility alleles is a
significant determinant of CRC pathogenesis. In this application, we propose 2 specific aims to study the
molecular interactions between a dietary carcinogen and a low-penetrance genetic variant of colorectal cancer.
In Aim 1, we will define the colon carcinogenesis profile of BaP and characterize colon tumor incidence in p53
polyadenylation signal mutant mice exposed to BaP. In Aim 2, we will dissect the molecular mechanisms
whereby BaP exposure contributes to colon carcinogenesis in human and mouse cells and in mice with the
p53 polyadenylation signal variant. With the completion of this project, we will have defined BaP as a novel
environmental risk factor and potentially a complete carcinogen for colorectal cancer in susceptible individuals.
We will understand the in vivo and in vitro function of the p53 variant in p53-mediated cellular processes and in
BaP-induced colon tumorigenesis and be able to expand these findings to future patient studies.

## Key facts

- **NIH application ID:** 10401445
- **Project number:** 5R01CA229080-06
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Yong Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $358,680
- **Award type:** 5
- **Project period:** 2019-10-16 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401445

## Citation

> US National Institutes of Health, RePORTER application 10401445, Dietary Carcinogens for Colorectal Cancer (5R01CA229080-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401445. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*