There are striking differences in colon cancer incidence and mortality between African Americans and other U.S. ethnic groups. Factors that impact on colon cancer risk and are modifiable by lifestyle-dietary factors may contribute to these differences. In particular, the insulin-IGF-axis has been implicated in insulin resistance and increased risk of several cancers. We evaluated the association between markers of insulin resistance and colon cancer. We also assessed whether they might explain the disparities in colon cancer incidence between African Americans and Whites. Participants were subjects enrolled in a population based case control study of colon cancer in North Carolina. The study included 231 African American and 297 Caucasian cases and 306 African American and 530 Caucasian controls frequency matched by age, race and sex. Consenting cases provided blood specimens, information about lifestyle and diet as well as anthropometric measures during in-home interviews. Plasma insulin, C-peptide, IGF-I, IGF-II, IGFBP-1, and IGFBP-3 were measured by enzyme immunoassays (ELISA). Mean plasma levels of insulin, C-peptide, IGF-I, IGF-II, IGFBP-1 and IGFBP-3 were compared between African colon cancer cases and controls for both racial groups by t-tests. Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (CI) while controlling for potential confounders such as age, sex, NSAIDs, and body mass index (BMI). Results: Compared to controls, African American and Caucasian cases were younger (p=0.0001) and reported higher energy intake (p=0.0001). African American cases were more likely to report low NSAIDs use (p=0.05) while Caucasians cases were more likely to report of higher percentage intake of daily calories from fat (p=0.01). When comparing the highest to the lowest quartile, IGF-I was associated with a 3 fold increased risk of colon cancer among African Americans (OR 3.2, 95% CI 1.9-5.3) and a 1.6 fold increased risk among Caucasians (OR 1.6, 95% CI 1.1-2.5). In both racial groups, elevated insulin (African Americans, OR 1.8, 95% CI 1.1-3.1; Caucasians OR 2.9, 95% CI 1.8-4.7) and C-peptide (African Americans, OR 2.0, 95% CI 1.2-3.3; Caucasians OR 2.5, 95% CI 1.7-3.9) were positively associated with colon cancer. We observed significant positive interactions between IGF-I, BMI and risk of colon cancer. Relative to low IGF-I and normal BMI, high IGF-I increased the risk of colon cancer in those who were overweight and obese (P interaction =0.03). Positive interactions were also observed for elevated IGF-I and low physical activity (P interaction =0.03). These findings provide evidence that markers of insulin resistance are associated with increased colon cancer risk in African Americans and Caucasians. The observed interactions for IGF-I/BMI and IGF-I physical activity suggests that lifestyle-dietary factors may modify the association between insulin resistance and colon cancer risk.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]