Date: 12 Jul 2011

Insulin, Insulin Resistance, and Cancer Associations

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Abstract

There have been long-standing attempts to elucidate the causes of cancer through observational research. While causation can never be definitively established based on this type of evidence, the impossibility of conducting experimental studies forces us to rely on epidemiologic studies to generate hypotheses regarding key risk factors for cancers. Initially, potential risk factors are considered based on biological hypo-theses, preliminary in vitro or animal studies, ecologic observations, or anecdotal evidence. Associations between risk factors and cancer outcomes are then sought through more rigorous observational studies. We must then determine whether such associations represent causative relationships, based on well-established criteria such as biologic plausibility, the strength, specificity and consistency of the association, temporality, and demonstration of a biologic gradient [1]. Recently, epidemiologic associations have emerged between obesity, diabetes, and certain forms of cancer such as those of the breast, colon, and pancreas. Since these conditions are associated with insulin resistance and compensatory hyperinsulinemia, it has been hypothesized that insulin may be a common mediator in these relationships due to its cancer-promoting properties. This chapter will review the growing body of evidence linking obesity and diabetes to the risk of certain cancers and the potential role of hyperinsulinemia in these associations, with a particular focus on cancer of the breast, colon, pancreas, and prostate. As a framework, this review consider these cancers separately, and will discuss the epidemiological evidence linking cancer risk first to obesity, then to insulin resistance and diabetes, followed by a discussion of direct and indirect evidence of the role of hyperinsulinemia in these associations.