Obesity and Cancer: How Understanding the Connection Early Can Have an Impact on Prevention

By Bhushan, Alok; Lai, James C. K. | Forum on Public Policy: A Journal of the Oxford Round Table, Spring 2008 | Go to article overview

Obesity and Cancer: How Understanding the Connection Early Can Have an Impact on Prevention


Bhushan, Alok, Lai, James C. K., Forum on Public Policy: A Journal of the Oxford Round Table


Introduction

When cells proliferate without restraints, there is development of cancer. Increased risk of cancer is observed in overweight children. However, the underlying cause and mechanism are unclear [1]. Thus, there is urgent need to investigate the cause-and-effect relationship between overweight children and their increased risk to developing cancer, with a long-term desirable goal of cancer prevention.

Cancer in Adolescent Years

Leukemia and brain cancers top the list of cancers in ages 0-16. There has been noticeable improvement in the survival of children with cancer. However, whether or not dietary habits and obesity in early years of life influence and predispose this segment of the population to developing cancer in future when they are older have not been systematically investigated. Nevertheless, obesity is linked to development of several types of cancers.

Role of obesity in cancer

Obesity is often linked to diabetes and heart diseases: on the other hand, there is considerable recent evidence linking obesity to cancer. Furthermore, diabetes itself increases the risk to developing cancer. For example, increase in carbohydrate intake and obesity parallels the increase in esophageal cancer. It has also been shown that 14% of deaths in men and 20% of deaths in women resulting from cancer at age 50 or older are due to obesity [5].

Association of obesity with prostate cancer has been reported by Quin and Babb (2002) [2]. Moreover, obesity may be a predictor of poor diagnosis at higher tumor grade and stage [3]. In the same studies, high waist to thigh circumference rather than body mass index (BMI) was associated with increased prostate cancer risk [2]. Adipokines that correlate with BMI enhance angiogenesis process which is critical in the progression of cancer [4].

Higher BMI also has been shown to increase the risk of breast cancer in post-menopausal women [6]. Mechanism underlying this risk is not well understood but has been suggested to be the consequence of increased secretion of estrogens. Increased risk of developing colon and rectal cancer is associated with increasing waist circumference whereas higher BMI only increased risk in men for rectal cancer [7, 8]. Several other studies link increased risk of cancer to obesity, BMI or waist-to-hip ratio (WHR) [9, 10, 12, 13, and 14]. Consequently, an improved understanding of the mechanisms underlying the biological linkage of obesity to cancer development and progression will throw new light the linkage.

Warburg Hypothesis and Cell Signaling: Systems Biological Approach

Within the context of our studies, it is relevant to note that the Kech School of Medicine, University of Southern California has been funded for 5 years to study relationships between obesity and cancer. The goal of their studies is to examine metabolic risk factors in obesity.

Considerable progress has been made in the area of understanding of differences between normal and cancer cells. Biological differences have led us to delineate mechanisms involved in progression of cancer. The multi-step mechanisms include mutations, clonal expansion of mutated cells, changes in gene expression, alteration in cell signaling, invasion, angiogenesis, and metastasis. These mechanisms involve carefully orchestrated biochemical pathways that are tuned by energy from cellular intermediary metabolism. The coordination of these pathways in a normal cell is disrupted by the environmental stress and in some cases genetic predispositions (e.g, obesity and diabetes). The ensemble adapts itself by favoring cellular milieu that leads to activation of pathways that favor progression of cancer.

The influence of the energetics in tumor genesis and progression was hypothesized by Warburg [11] who showed increase in aerobic glycolysis and dependence of the glycolytic pathway for production of ATP. This phenomenon is known as the Warburg effect. …

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