Hyperinsulinemia, Insulin Resistance, Vitamin D, and Colorectal Cancer Among Whites and African Americans

African Americans have the highest incidence and mortality rates of colorectal cancer among all US racial and ethnic groups. Dietary factors, lifestyle factors, obesity, variability in screening rates, socioeconomic differences, barriers to screening, and differences in access to health care may be contributory factors to racial and ethnic disparities. African Americans are more likely to demonstrate microsatellite instability in their colorectal tumors leading to malignancy. However, these differences do not completely explain all the variances. Ample evidence implicates insulin resistance and its associated conditions, including elevated insulin and insulin-like growth factor-1 (IGF-1), in colorectal carcinogenesis. African Americans have a high risk for and a high prevalence of insulin resistance and subsequent overt type 2 diabetes. Recent clinical studies revealed that ethnic differences between whites and African Americans in early diabetes-related conditions including hyperinsulinemia already exist during childhood. African Americans have a much higher prevalence of vitamin D deficiency than whites throughout their life spans. Vitamin D deficiency has been associated with higher rates of diabetes and colorectal cancer, particularly in individuals with high serum insulin and IGF-1 levels. Moreover, African Americans have lower insulin sensitivity in tissues, independent of obesity, fat distribution, and inflammation. Further development of measures of biomarkers of tumor biology and host susceptibility may provide further insight on risk stratification in African Americans.