Topic: NCI Provocative Questions

How does obesity contribute to cancer risk?

Background: While many studies have documented an increased risk of cancer incidence and mortality in individuals who are obese, the mechanisms that underlie this risk remain poorly understood. Successful applications for this question will identify and study molecular mechanisms that are induced by obesity and that are essential for some aspect of tumor development. Key issues for study include: What molecular changes induced by obesity actually promote cancer development? Can we describe these changes in ways that will allow a mechanistic link between risk and cancer cell biology? Are the risks reversible as some data suggest and, if so, by what mechanism?

Feasibility: Recent studies of the endocrinology of eating disorders, the metabolic correlates of fat accumulation, the pathogenic consequences of obesity (such as diabetes mellitus), and the development of powerful molecular profiling methodologies have created opportunities for understanding the relationship of obesity to carcinogenesis at a mechanistic level. Relevant research could include molecular studies to identify metabolic and signaling pathways associated with obesity. Studies on the genetics of obesity may be helpful in identifying key regulatory pathways that may link to cancer development.

Implications of success: A deeper understanding of the mechanisms of the cancer risk posed by obesity could suggest new strategies for countering these risks. Understanding how obesity is mechanistically linked to cancer development would bridge epidemiologic identification of risk factors with the molecular biology of cancer development. This would be a remarkable confluence of two exceptionally important cancer research disciplines and would potentially lead to many more studies that could elucidate mechanisms of obesity-related cancer pathogenesis.

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