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

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 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.

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 as a 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 SARIFA-specific 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.