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Effects of Diet and Advanced Glycation-End (AGE) Products on the Incidence of Colorectal Cancer

Principal Investigator
Name
Ru Chen
Degrees
Ph.D.
Institution
Baylor College of Medicine
Position Title
PI
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-1919
Initial CDAS Request Approval
Jun 25, 2025
Title
Effects of Diet and Advanced Glycation-End (AGE) Products on the Incidence of Colorectal Cancer
Summary
Advanced glycation end-products (AGEs), formed through the non-enzymatic reaction between sugars and proteins or lipids, are increasingly recognized as contributors to carcinogenesis, including colorectal cancer. Dietary intake is a major source of AGEs, particularly from foods that are processed or cooked at high temperatures. However, several prior prospective studies examining the association between dietary AGEs and cancer incidence have yielded inconsistent findings. To address this gap, we propose using the epidemiologic and dietary data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to investigate the association between dietary patterns, estimated AGE intake, and colorectal cancer risk.
This study will involve a secondary analysis of the PLCO database, which includes dietary information from the validated Diet History Questionnaire, baseline health characteristics, and longitudinal cancer outcome data. We will estimate individual AGE exposure based on established AGE content databases linked to reported dietary intake. Participants with incomplete dietary data or pre-existing colon cancer at baseline will be excluded.
Primary objectives include: (1) evaluating the association between estimated dietary AGE intake and colorectal cancer incidence, and (2) exploring whether specific dietary patterns (e.g., high red meat intake, low fruit/vegetable intake) interact with AGE exposure to modify colon cancer risk. Multivariable Cox proportional hazards models will be used, adjusting for known confounders such as age, sex, race, BMI, smoking status, physical activity, family history of colorectal cancer, and total energy intake.
Secondary analyses will assess whether the association between dietary AGEs and colorectal cancer varies by demographic subgroups or lifestyle factors, and whether there are dose-response relationships. We also plan sensitivity analyses excluding early incident cases to minimize reverse causation.
By leveraging the large sample size, detailed dietary data, and long follow-up of the PLCO cohort, this project aims to provide novel insights into the dietary drivers of colorectal cancer, particularly focusing on AGEs. Results could inform dietary recommendations and prevention strategies targeting modifiable risk factors to reduce the burden of colon cancer.
Aims

Colorectal cancer is a leading cause of cancer-related morbidity and mortality, and evidence suggests that diet plays a crucial role in modulating risk. Advanced glycation end-products (AGEs), abundant in processed and high-temperature cooked foods, have been implicated in cancer development through pro-inflammatory and oxidative stress pathways. However, few large-scale prospective studies have evaluated the impact of dietary AGE intake on colorectal cancer incidence. Using the PLCO Cancer Screening Trial database, we aim to investigate the role of diet and AGEs in colorectal cancer development.

Our Specific Aims are:
● Aim 1: Quantify dietary AGE intake among PLCO participants.
Using data from the Diet History Questionnaire (DHQ), we will estimate individual AGE consumption by linking reported food intake to established AGE food content databases. This will allow us to create an AGE exposure variable for each participant.

● Aim 2: Determine the association between dietary AGE intake and colon cancer incidence.
We will use multivariable Cox proportional hazards regression models to assess the relationship between estimated dietary AGE intake and the risk of developing colon cancer, adjusting for confounding variables such as age, sex, BMI, smoking status, physical activity, family history, and total energy intake.

● Aim 3: Identify dietary patterns associated with high AGE intake and evaluate their interaction with colon cancer risk.
We will analyze dietary patterns, focusing on consumption of high-AGE foods such as red meat, processed foods, and fried items. We will investigate whether these patterns modify the relationship between overall AGE intake and colon cancer incidence.

● Aim 4: Perform subgroup analyses to explore effect modification by demographic and lifestyle factors.
We will assess whether the association between dietary AGEs and colon cancer varies by key factors such as age group, sex, race/ethnicity, diabetic status, BMI category, and smoking status.

● Aim 5: Explore dose-response relationships and conduct sensitivity analyses.
We will test for a dose-response association between dietary AGE intake and colon cancer risk and perform sensitivity analyses excluding cases diagnosed within the first two years to account for potential reverse causation.

Impact:
Findings from this study will clarify the role of dietary AGEs in colon carcinogenesis and identify high-risk dietary patterns. This work could help inform future dietary guidelines and cancer prevention strategies targeting modifiable exposures.

Collaborators

Saager Chawla, Baylor College of Medicine
Dr. Ru Chen, Baylor College of Medicine