Tissue-Specificity and Ethnic Diversity in Obesity-Related Risk of Cancer May Be Explained by Variability in Insulin Response and Insulin Signaling Pathways

Abstract

Obesity is a predisposing risk factor for several chronic diseases. The link between obesity and cancer appears to be particularly complex. Notably only the risk for development of specific cancers appear to be affected. Moreover, the obesity-related risk of cancer is very different across ethnic groups. African-Americans appear particularly prone, whereas Hispanics appear to be relatively protected. Obesity is associated with increased levels of circulating insulin. These levels of elevated insulin may serve to promote proliferation of fat cells to accommodate the elevated nutrient flux. However, elevated levels of insulin may be a major mediating factor influencing cancer risk. This hypothesis alone cannot explain the complexity of the phenomenon. We suggest here that the different insulin responses to obesity of different ethnic groups may explain their different risk profiles. Moreover, we speculate that tissue-specific variations in the insulin signaling pathways may underlie their differential susceptibility to tumorigenesis in the face of elevated obesity. Elevated cancer risk may be an unwanted side effect of insulin responding to elevated nutrient flux in the obese which it serves to proliferate fat cells that provide a location for storage of ingested fat, which consequently prevents ectopic fat storage. Hence, while Hispanics may be protected from cancer risk in obesity because of their lower insulin response, they have an elevated risk of fatty liver disease. Reduction of insulin levels in obesity as a strategy to reduce cancer risk may pose additional problems unless it is combined also with interventions that aim to limit nutrient influx.