# Obesity, sedentary behaviors, and diet quality for prevention and early detection of early-onset colorectal neoplasia

> **NIH NIH R37** · WASHINGTON UNIVERSITY · 2020 · $664,712

## Abstract

PROJECT SUMMARY/ABSTRACT
The rising incidence in early-onset colorectal cancer (CRC diagnosed before 50), has resulted in updated
American Cancer Society (ACS) guideline advising average-risk screening begin at age 45, rather than 50.
Debates centered around the substantial cost and resources of adding 21 million adults at very low risk to the
screening pool, and “further personalize screening strategies” was a priority. Identifying the contributors of the
rising incidence are the first steps but thus far an unmet need. Lifestyle factors that preceded and mirrored the
rapid rise of early-onset CRC, including obesity, prolong sitting, and poor diet, may play a critical role. Our
preliminary data support the importance of obesity and sedentary behaviors and early-onset CRC are more likely
to be processed from traditional adenoma-carcinoma sequence compared to CRC diagnosed after age 65.
Therefore, investigation into risk factors for early-onset advanced adenoma, the major targets of screening, will
illuminate insights of colorectal carcinogenesis at younger ages. Accumulating data suggest that microbial
translocation/endotoxemia, which triggers subsequent inflammation and immune response, and augmented by
above-mentioned lifestyle factors, might be an emerging pathway. We hypothesized that obesity, prolonged
sitting, and poor diet quality increase risk of early-onset advanced adenoma through increasing endotoxemia
and inflammation, and contribute to the rise of early-onset CRC. To test these hypotheses, we will leverage
lifestyle data collected throughout life course in two well-characterized prospective cohort (Nurses’ Health Study
II [NHSII]) and Southern Community Cohort Study (SCCS) with archived pre-diagnostic blood, complemented
by decision modeling using the Microsimulation Screening Analysis‐Colon (MISCAN‐Colon), the model used to
inform the ACS screening guideline. Specifically, we will first examine prospectively the associations between
mid-adulthood and early-life obesity, sedentary behaviors, and diet quality and risk of early-onset advanced
adenoma (Aim 1). We will then investigate into the independent and mediating role of pre-diagnostic plasma
markers of endotoxemia and inflammation in early-onset neoplasia, leveraging a cost-efficient and reliable
proteomic platform. Such profiling will also allow for untargeted discoveries of protein-protein interactions to
identify novel networks/targets (Aim 2). Finally, we will conduct a meta-analysis to identify early-onset CRC
specific risk factors and quantify the relative risks, and integrate these findings to the MISCAN-Colon to estimate
the contributions of secular changes of lifestyle to the rise of early-onset CRC and to improve the simulations
used to support the 2018 ACS screening guideline using early-onset CRC specific risk factors/estimates (Aim
3). Our established team, led by an early stage investigator focused on early-onset CRC, and leaders in
epidemiology, bioinformatics, biom...

## Key facts

- **NIH application ID:** 10051712
- **Project number:** 1R37CA246175-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Yin Cao
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $664,712
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051712

## Citation

> US National Institutes of Health, RePORTER application 10051712, Obesity, sedentary behaviors, and diet quality for prevention and early detection of early-onset colorectal neoplasia (1R37CA246175-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10051712. Licensed CC0.

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