Mucosal Inflammation and Risk of Colorectal Adenomas

Colorectal cancer is the second leading cause of cancer death in the United States. In this study, the association between colonic inflammation and adenomas was determined. It was hypothesized that elevated expression of mucosal inflammatory markers would be associated with an increased risk of colorectal adenomas. Assessment and association of increased natural killer (NK) cells in the colonic mucosa and local mRNA expression of IL‐6, IL‐10, IL‐17 and TNF‐α with adenomas and known risk factors such as body mass index and waist‐hip ratio (WHR) were conducted and examined. Using immunohistochemistry and reverse‐transcriptase PCR, local cytokine gene expression and abundance of NK cells in 50 adenoma cases and 50 non‐adenoma controls were assessed. Logistic regression and t‐tests were employed to evaluate differences between cases and controls. Overall, compared to controls, cases were more likely to be males (p=0.02) and cases also had a higher WHR than controls (p=0.0001). An inverse association between IL‐10 and adenomas was observed. Compared to those with low IL‐10 levels, subjects with high IL‐10 gene expression were less likely to be cases (OR 0.22, 95% CI 0.08–0.62). Although there was no statistically significant association between CD57 positivity (NK cells) and risk of adenomas, there was a weak positive correlation between IL‐10 gene expression and NK cells. A borderline positive correlation between WHR and CD57 positivity (p=0.08) was observed. These results show that reduced IL‐10 gene expression, increased NK cells and WHR are linked with adenomas. These findings implicate specific aspects of local inflammation in the etiology of colorectal adenomas. Supported, in part, by grants from the NIH: R01 CA136887, R01 CA44684, P30 DK 34987, P50 CA 106991 and 5R25GM063775