# Examining Early Life Risk Factors and Patterns of Screening for Early-Onset Colorectal Cancer

> **NIH NIH F31** · YALE UNIVERSITY · 2024 · $40,742

## Abstract

PROJECT SUMMARY/ABSTRACT
 In the United States (US), the incidence of early-onset colorectal cancer (EOCRC), defined as colorectal
cancer (CRC) diagnosed among individuals <50 years of age, has been increasing rapidly. Compared to late-
onset CRC (i.e., CRC diagnosed among individuals ≥50 years of age), EOCRC is characterized by more
aggressive pathology and distinct genetic profiles, indicating that the etiology of EOCRC may be distinct. There
have been a limited number of studies examining the risk factors of EOCRC, and none have focused on early
life risk factors, which could be particularly relevant to early-onset diseases. Over the past few years, the
American Cancer Society and the US Preventative Services Task Force reduced the recommended age of CRC
screening from 50 years to 45 years, and the COVID-19 pandemic influenced the provision of preventative
services across the country. These events could impact the temporal and geographic patterns of screening for
EOCRC, but no study has systematically assessed such impacts in a large sample of the US population. The
proposed study aims to 1) identify early-life risk factors of EOCRC and 2) evaluate spatiotemporal patterns of
EOCRC screening in the US. For the first aim, we will conduct a nested case-control study within the California
birth cohort and compare the birth characteristics between 1200 EOCRC cases and 60,000 control subjects
matched on year of birth. In addition, we will obtain birth address matched social, behavioral, lifestyle, and
environmental factors from the Centers for Disease Control and Prevention and the Environmental Protection
Agency and compare these neighborhood-level factors between the 1,200 cases and 60,000 controls. Two key
methodological challenges will be addressed: a) spatial autocorrelation, the tendency of adjacent geographic
units to share similar attributes; b) the modifiable areal unit problem, a biasing effect that occurs when observed
associations between exposures and outcomes vary based on the scale of the chosen geographic unit. For the
second aim, we will assess temporal patterns in EOCRC screening and identify factors associated with potential
regional variation in screening by leveraging unique claims data from Blue Cross Blue Shield (BCBS), the largest
insurance provider in the US that covers one-third of all Americans. Approximately 4 million beneficiaries aged
45-49 years are enrolled in BCBS each year, allowing us a great opportunity to assess both stool-based and
structural CRC screening tests. With a rigorous design and unparalleled sample sizes, the proposed study
addresses research questions with clear public health significance, is very innovative, and will probably yield a
high impact on our knowledge about the etiology and screening of EOCRC – a critically understudied field
according to the National Cancer Institute. In addition, by bringing together a multidisciplinary team of experts in
cancer epidemiology, health services research, s...

## Key facts

- **NIH application ID:** 10997307
- **Project number:** 5F31CA281335-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Sunny Siddique
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,742
- **Award type:** 5
- **Project period:** 2023-08-18 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997307

## Citation

> US National Institutes of Health, RePORTER application 10997307, Examining Early Life Risk Factors and Patterns of Screening for Early-Onset Colorectal Cancer (5F31CA281335-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10997307. Licensed CC0.

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