Excess Weight, Polygenic Risk Score, and Findings of Colorectal Neoplasms at Screening Colonoscopy

Q: What was the study designed to assess?

The study assessed independent and joint associations of excess weight and polygenic risk scores with colorectal neoplasm prevalence, including non-advanced and advanced adenomas, in a screening colonoscopy cohort.

Q: How did excess weight relate to colorectal neoplasm risk?

Overweight and obesity were associated with increased risk of any colorectal neoplasm, and obesity was additionally associated with increased risk of advanced colorectal neoplasm.

Q: Did polygenic risk interact with BMI?

No interaction between BMI and polygenic risk scores was observed, indicating multiplicative effects of both factors rather than an interaction.

Sep 21, 2026

Uploaded by Asher

Excess weight is an established risk factor for colorectal cancer, but its stage-specific impact alongside polygenic risk remains unclear. In 4,784 screening-colonoscopy participants, body mass index and polygenic risk scores were analyzed for associations with colorectal neoplasm findings. Overweight and obesity increased risk of any neoplasm, while obesity increased advanced neoplasm risk. Polygenic risk showed stronger dose-response for advanced disease. No BMI–PRS interaction was observed, suggesting multiplicative effects. Genetic risk equivalent modeling showed the obesity impact compares to substantially higher PRS percentiles.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Introduction

Methods

Results

Discussion

Keywords

ARTICLE 1913 | INTRODUCTION: Excess weight is an established risk factor of colorectal cancer (CRC) . However, evidence is lacking on
how its impact varies by polygenic risk at different stages of colorectal carcinogenesis.
METHODS: We assessed the individual andjoint associations of body mass index(BMI)and polygenic risk scores(PRSs) with findings of colorectal neoplasms among 4,784 participants of screening colonoscopy. Adjusted odds ratios (aORs) for excess weight derived by multiple logistic regression were converted to genetic risk equivalents (GREs) to quantify the impact of excess weight compared with genetic predisposition.
RESULTS: Overweight and obesity (BMI 25–<30 and‡30 kg/m2) were associated with increased risk of any colorectal neoplasm (aOR [95% confidence interval, CI] 1.26 [1.09–1.45] and 1.47 [1.24–1.75]). Obesity was associated with increased risk of advanced colorectal neoplasm (aOR [95% CI] 1.46 [1.16–1.84]). Doseresponse relationships were seen for the PRS (stronger for advanced neoplasms than any neoplasms), with no interaction with BMI, suggesting multiplicative effects of both factors. Obese participants with a PRS in the highest tertile had a 2.3-fold (95% CI 1.7–3.1) and 2.9-fold (95% CI 1.9–4.3) increased risk of any colorectal neoplasm and advanced colorectal neoplasm, respectively. The aOR of obesity translated into a GRE of 38, meaning that its impact was estimated to be equivalent to the risk caused by 38 percentiles higher PRS for colorectal neoplasm.
DISCUSSION: Excess weight and polygenic risk are associated with increased risk of colorectal neoplasms in a multiplicative manner. Maintaining normal weight is estimated to have an equivalent effect as having
38 percentiles lower PRS.
KEYWORDS: colorectal neoplasm; body mass index; polygenic risk score; genetic risk equivalent
SUPPLEMENTARY MATERIAL accompanies this paper at [http://links.lww.com/AJG/D282](http://links.lww.com/AJG/D282) | | | --- | --- | | Am J Gastroenterol 2024;119:1913–1920. [https://doi.org/10.14309/ajg.0000000000002853](https://doi.org/10.14309/ajg.0000000000002853) | | | INTRODUCTION
In the past decades, the prevalence of obesity has escalated, reaching a pandemic level (1,2) . Being overweight or obese increases the risk of multiple chronic diseases including multiple cancers and is associated with lower quality of life and a reduced life span (3) . Excess weight is an established risk factor of colorectal cancer (CRC) (4–6), the third most commonly diagnosed cancer and the second leading cause of cancer-related mortality worldwide (7) . The slow progression of most colorectal neoplasms via the adenoma-carcinoma sequence, typically spanning at least 10 years (8), oﬀers opportunities of prevention through lifestyle modiﬁcations and early detection and intervention. | Studying how genetic and environmental factors interact with each other can help reveal the mechanisms of colorectal carcinogenesis(9). Furthermore, joint consideration ofboth factors maybe helpful for targeted eﬀorts of prevention. In recent years, polygenic risk scores (PRSs), integrating information from genetic variants found in genome-wide association studies (GWASs), have become useful tools to measure individuals’ genetic risk ofCRC (10,11) . It has been shown that PRSs may complement and substantially improve CRC risk classiﬁcation based on known factors such as lifestyle and family history (12–14) . Besides CRC, PRSs have also been shown to exhibit associations with the prevalence ofadvanced adenomas, the precursor of most CRCs (15). Previous work has explored individual and joint associations of excess weight and a | Excess Weight, Polygenic Risk Score, and Findings of Colorectal Neoplasms at Screening Colonoscopy Ruojin Fu, MMed1 ,2, Xuechen Chen, PhD1 ,3, Tobias Niedermaier, PhD1, Teresa Seum, MSc1 ,2, Michael Hoffmeister, PhD1 and Hermann Brenner, MD, MPH1 ,4 ,5 COLON 1Division of Clinical Epidemiology and Aging

FAQs

What was the study designed to assess?

The study assessed independent and joint associations of excess weight and polygenic risk scores with colorectal neoplasm prevalence, including non-advanced and advanced adenomas, in a screening colonoscopy cohort.

How did excess weight relate to colorectal neoplasm risk?

Overweight and obesity were associated with increased risk of any colorectal neoplasm, and obesity was additionally associated with increased risk of advanced colorectal neoplasm.

Did polygenic risk interact with BMI?

No interaction between BMI and polygenic risk scores was observed, indicating multiplicative effects of both factors rather than an interaction.

Sep 21, 2026

Uploaded by Asher