The metabolic syndrome: A high-risk state for cancer?

Abstract

The metabolic syndrome is composed of cardiovascular risk factors including increased body mass index/waist circumference, blood pressure, plasma glucose, and triglycerides, as well as decreased high-density lipoprotein cholesterol. The essence of the metabolic syndrome lies in the clustering of these risk factors, which are associated with cardiovascular disease. Interestingly, most of the components of the metabolic syndrome have individually been linked in some way to the development of cancer. However, epidemiological studies linking the metabolic syndrome to cancer are scarce. Nevertheless, two such studies indicate that the clustering of metabolic syndrome components significantly increases the risk of colon cancer mortality compared with the individual components. The purpose of this review is to further explore the potential relationship between the metabolic syndrome and cancer risk. Specifically, we examine the hypothesis that individual components of the metabolic syndrome contribute to the development of several processes, including insulin resistance, aromatase activity, adipokine production, angiogenesis, glucose utilization, and oxidative stress/DNA damage, which can work together to increase cancer risk beyond that of the individual components alone. We propose that the metabolic syndrome be considered as a high-risk state for certain types of cancer and that this relationship should be systematically explored across cancer types.

Figure 1

Diagram of factors linking the MS with cancer development. Plasma glucose, BMI/waist circumference, and triglycerides/FFA affect different complementary processes that can work together to promote cancer development/growth. Additional characteristics of the MS, such as increased HDL and hypertension, are also correlated with cancer growth, but a direct mechanism for these associations has not been confirmed. Abbreviations: E, estrone; E₂, estradiol; A, androgens; mito, mitochondria; ROS, reactive oxygen species; SHBG, sex hormone-binding globulin; FFA, free or nonesterified fatty acids; TG, triglycerides; IGFBPs, insulin-like growth factor-binding proteins.