Obesity and cancer: mechanistic insights from transdisciplinary studies

Abstract

Obesity is associated with a range of health outcomes that are of clinical and public health significance, including cancer. Herein, we summarize epidemiologic and preclinical evidence for an association between obesity and increased risk of breast and prostate cancer incidence and mortality. Moreover, we describe data from observational studies of weight change in humans and from calorie-restriction studies in mouse models that support a potential role for weight loss in counteracting tumor-promoting properties of obesity in breast and prostate cancers. Given that weight loss is challenging to achieve and maintain, we also consider evidence linking treatments for obesity-associated co-morbidities, including metformin, statins and non-steroidal anti-inflammatory drugs, with reduced breast and prostate cancer incidence and mortality. Finally, we highlight several challenges that should be considered when conducting epidemiologic and preclinical research in the area of obesity and cancer, including the measurement of obesity in population-based studies, the timing of obesity and weight change in relation to tumor latency and cancer diagnosis, and the heterogeneous nature of obesity and its associated co-morbidities. Given that obesity is a complex trait, comprised of behavioral, epidemiologic and molecular/metabolic factors, we argue that a transdisciplinary approach is the key to understanding the mechanisms linking obesity and cancer. As such, this review highlights the critical need to integrate evidence from both epidemiologic and preclinical studies to gain insight into both biologic and non-biologic mechanisms contributing to the obesity-cancer link.

Keywords: NSAIDs; aspirin; breast cancer; cholesterol; epidemiology; insulin; mechanisms; metformin; mouse models; obesity; prostate cancer; screening; statins; transdisciplinary; weight loss.

Figure 1

Using a transdisciplinary approach to study mechanisms linking obesity and cancer.

Figure 2

Non-biologic mechanisms linking obesity and cancer mortality.

Figure 3

Putative mechanisms linking obesity with cancer risk and progression: lessons from studies of chemopreventive agents

Figure 4

Computed tomography (CT) scans of two individuals with similar waist circumference (WC) but different amounts of visceral and subcutaneous fat area, illustrating the potential for misclassification when using WC as a surrogate of visceral obesity.

Figure 5

Challenges associated with studying obesity: defining the exposure, and potential confounders.