Energy Balance-Related Factors and Direct Tumor-Adipocyte Contact in Colorectal Cancer: Etiologic Insights from the...

Stroma AReactive Invasion Front Areas (SARIFA) are a histopathologic biomarker characterized by a direct tumor-adipocyte contact at the tumor invasion front. Although the tumor-promoting 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.

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 as a proxy for waist circumference, and nonoccupational physical activity and colon and rectal cancer risk by SARIFA status.

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 SARIFA-specific patterns in men or for rectal cancer.

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.

This study extends previous epidemiologic findings by suggesting that adiposity may influence colon cancer development, resulting in a specific tumor-stroma interaction phenotype.