Energy Balance-Related Factors and Direct Tumor–Adipocyte Contact in Colorectal Cancer - Etiologic Insights from the Population-Based Netherlands Cohort Study

Sep 22, 2026

Energy balance-related prediagnostic factors and their link to a specific tumor microenvironment phenotype were examined in colorectal cancer. Stroma AReactive Invasion Front Areas (SARIFA) reflect direct tumor–adipocyte contact at the invasion front. Using Netherlands Cohort Study data (120,852 participants; 1,826 incident cases with known SARIFA status), Cox regression assessed baseline BMI, lower-body clothing size as a waist proxy, and nonoccupational physical activity by SARIFA status. Results showed stronger BMI associations with SARIFA-positive colon cancer in men, inverse physical activity effects in women for SARIFA-positive disease, and weaker or less consistent patterns otherwise.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Background

Methods

Results

Conclusions

Impact

Introduction

Energy Balance–Related Factors and Direct Tumor–Adipocyte Contact in Colorectal Cancer: Etiologic Insights from the Population-Based Netherlands Cohort Study Kelly Offermans1, Nic G. Reitsam2,3, Bianca Grosser2,3,4, Jessica Zimmermann2, Heike I. Grabsch5,6, Colinda C.J. M. Simons7, Piet A. van den Brandt1,7, and Bruno Mrkl2,3 | | | A | | B | S | | T | R | | A | | C | T | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Background: Stroma AReactive Invasion Front Areas (SARIFA) are a histopathologic biomarker characterized by a direct tumor– adipocyte contact at the tumor invasion front. Although the tumorpromoting effect of tumor–adipocyte interactions has often been linked to obesity, it is unclear whether prediagnostic energy balance–related factors are differentially associated with the risk of SARIFA-positive versus SARIFA-negative colorectal cancers.
Methods: We analyzed data from the Netherlands Cohort Study, including 120,852 participants and 1,826 incident colorectal cancer cases with known SARIFA status. Multivariable-adjusted Cox regression was used to estimate associations between baseline prediagnostic body mass index (BMI), lower-body clothing size asa proxy for waist circumference, and nonoccupational physical activity and colon and rectal cancer risk by SARIFA status.
Results: In men, BMI was more strongly associated with the risk of SARIFA-positive colon cancer [hazard ratio (HR) per
􀀶 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 5 kg/m2, 1.57; 95% confidence interval (CI), 1.20–2.07] than SARIFA-negative tumors (HR, 1.22; 95% CI, 1.01–1.48), with similar patterns for lower-body clothing size. In women, weaker associations were observed, but estimates were again higher for SARIFA-positive tumors than SARIFA-negative tumors. Physical activity was inversely associated with SARIFA-positive colon cancer in women (HR per 30 minutes/day, 0.92; 95% CI, 0.85– 1.01), but not SARIFA-negative tumors, with no clear SARIFAspecific patterns in men or for rectal cancer.
Conclusions: Findings suggest a stronger role of body fatness in the development of SARIFA-positive than SARIFA-negative colon cancer and provide novel evidence warranting confirmation in other molecular pathologic epidemiology studies.
Impact: This study extends previous epidemiologic findings by suggesting that adiposity may influence colon cancer development, resulting in a specific tumor–stroma interaction phenotype. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | 1Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center+, Maastricht, the Netherlands. 2Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany. 3Bavarian Cancer Research Center (BZKF), Augsburg, Germany. 4Institute of Pathology, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany. 5Department of Pathology, GROW-Research Institute for Oncology and Reproduction, Maas

FAQs

What is SARIFA in colorectal cancer research?

SARIFA refers to Stroma AReactive Invasion Front Areas, a histopathologic biomarker defined by direct tumor–adipocyte contact at the tumor invasion front.

Which prediagnostic energy balance factors were analyzed?

Baseline BMI, lower-body clothing size as a proxy for waist circumference, and nonoccupational physical activity were assessed in relation to colorectal cancer risk by SARIFA status.

What did the study find about BMI and SARIFA-positive tumors?

In men, BMI showed a stronger association with SARIFA-positive colon cancer than with SARIFA-negative tumors, with similar patterns for lower-body clothing size.

Sep 22, 2026

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