Obesity and cancer risk: evidence, mechanisms, and recommendations

Abstract

Obesity, a growing health problem worldwide, has been associated with the metabolic syndrome, diabetes, cardiovascular disease, hypertension, and other chronic diseases. Recently, the obesity-cancer link has received much attention. Epidemiological studies have shown that obesity is also associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment and increased cancer-related mortality. Biological mechanisms underlying the relationship between obesity and cancer are not well understood. They include modulation of energy balance and calorie restriction, growth factors, multiple signaling pathways, and inflammatory processes. Key among the signaling pathways linking obesity and cancer is the PI3K/Akt/mTOR cascade, which is a target of many of the obesity-associated factors and regulates cell proliferation and survival. Understanding the molecular and cellular mechanisms of the obesity-cancer connection is important in developing potential therapeutics. The link between obesity and cancer underscores the recommendation to maintain a healthy body weight throughout life as one of the most important ways to protect against cancer.

Figure 1

Energy metabolism. Obesity increases circulating leptin, available IGF-1, and proinflammatory cytokines, leading to increased signaling through the PI3K/Akt cascade. These signals converge on mTOR, promoting cell proliferation and inhibiting apoptosis. Conversely, caloric restriction enhances signaling through AMPK, suppressing mTOR activity and promoting cancer cell death.