Background Dysregulated insulin signaling is thought to contribute to cancer risk. Methods To determine if insulin-related serum factors are associated with colon polyps, 126 asymptomatic men (48–65yr) were recruited at colonoscopy. Blood was collected. Odds ratios were determined using polytomous logistic regression for polyp number and type. Results Males with serum C-peptide concentration >3.3 ng/ml were 3.8 times more likely to have an adenoma relative to no polyp than those with C-peptide ≤1.8 ng/ml. As C-peptide tertile increased, an individual was 2 times more likely to have an adenoma (p=0.01) than no polyp. There were no associations between insulin-like growth factor or its binding proteins with polyp number or type. Males with soluble receptor for advanced glycation end products (sRAGE) concentration >120.4 pg/ml were 0.25 times less likely to have ≥3 polyps relative to no polyps compared to males with sRAGE ≤94.5 pg/ml. For each increase in sRAGE tertile, a man was 0.5 times less likely to have ≥3 polyps than no polyps (p=0.03). Compared to males with a serum vascular endothelial growth factor (VEGF) concentration ≤104.7 pg/ml, males with a serum VEGF concentration >184.2 pg/ml were 3.4 times more likely to have ≥3 polyps relative to no polyps. As the VEGF tertile increased, a man was 1.9 times more likely to have ≥3 polyps than no polyps (p=0.049). Conclusions Serum concentrations of C-peptide, sRAGE, and VEGF may indicate which men could benefit most from colonoscopy. Impact Identification of biomarkers could reduce medical costs through the elimination of colonoscopies on low-risk individuals.

Chronic inflammation contributes to colorectal carcinogenesis. To determine if serum cytokines are associated with colon polyps, 126 asymptomatic men (48–65yr) were recruited at colonoscopy. Serum cytokine concentrations were measured. Odds ratios were determined using polytomous logistic regression for polyp number and type. Males with serum monocyte chemotactic protein-3 (MCP-3) or soluble interleukin-4 receptor (sIL-4R) concentrations in the highest tertile were 0.2 times less likely to have ≥3 polyps relative to no polyps. For each increase in serum MCP-3 or sIL-4R tertile a man was about 0.4 times less likely to have ≥3 polyps than no polyps. Males with serum concentrations of interferon-α2 (IFN-α2) or interleukin (IL)-7 in the highest tertile were 3 times more likely to have an adenoma relative to no polyps. Those with serum IL-8 concentrations in the highest tertile were 4 times more likely to have an adenoma relative to no polyps. For each increase in serum IFN-α2, IL-7 or IL-8 tertile an individual was 1.8 times more likely to have an adenoma than no polyp. Serum concentrations of MCP-3, sIL-4R, IFN-α2, IL-7 and IL-8 may indicate which men are more likely to have colorectal polyps.

Activation of the insulin ‐‐ insulin‐like growth factor (IGF) signaling axis is hypothesized to increase colon cancer risk. The aim of this study was to determine if serum factors related to insulin or insulin signaling were associated with advanced colon polyps in males. 126 men (48 ‐ 65 yr) were recruited at time of colonoscopy, and blood was collected. Odds ratios were determined using logistic regression for polyp number and polytomous logistic regression for polyp severity. 29% of the men in our study had a tubular adenoma. Participants with C‐peptide levels above 3.3ng/ml were 3.8 (CI: 1.3 ‐ 11.1) times more likely than those with C‐peptide levels less than 1.8ng/ml to have a tubular adenoma. For each category increase in C‐peptide, an individual was 2.0 (CI: 1.2 ‐ 3.4) times more likely to have a tubular adenoma than no polyp. Those individuals with serum soluble receptor for advanced glycation end products (sRAGE) greater than 120.4pg/ml were 0.3 (CI: 0.1 ‐ 0.9) times less likely than those with sRAGE lower than 94.5pg/ml to have 蠅3 polyps than no polyps. For each category increase in sRAGE, an individual was 0.5 (CI: 0.3 ‐ 0.9) times less likely to have 蠅3 polyps than no polyps. Other factors, such as insulin growth factor binding proteins, were not associated with polyp presence or severity in this population. Serum C‐peptide levels are a potential biomarker of polyp severity in white males. Grant Funding Source: Supported by NCI 1R03CA142000 and MSU CTSI

Chronic inflammation contributes to colorectal carcinogenesis. To determine if serum cytokines are associated with colon polyps, 126 asymptomatic men (48–65yr) were recruited at colonoscopy. Serum cytokine concentrations were measured by multiplex immunoassay. Odds ratios were determined using polytomous logistic regression for polyp number and type. Males with serum monocyte chemotactic protein‐3 (MCP‐3) or soluble interleukin‐4 receptor (sIL‐4R) concentrations in the lowest tertile were 5 times more likely to have 蠅3 polyps relative to no polyps. For each decrease in serum MCP‐3 or sIL‐4R tertile a man was about 2.5 times more likely to have 蠅3 polyps than no polyps. Males with serum concentrations of interferon‐α2 (IFN‐α2) or interleukin (IL)‐7 in the highest tertile were 3 times more likely to have an adenoma relative to no polyps. Those with serum IL‐8 concentrations in the highest tertile were 4 times more likely to have an adenoma relative to no polyps. For each increase in serum IFN‐α2, IL‐7 or IL‐8 tertile an individual was 1.8 times more likely to have an adenoma than no polyp. Serum concentrations of MCP‐3, sIL‐4R, IFN‐α2, IL‐7 and IL‐8 may indicate which men are more likely to have colorectal polyps and could therefore most benefit from colonoscopy. Support: NIH R03CA142000, MSU Clinical & Translational Sciences Institute