Obesity's Effect on Cancer Risk
Obesity's Effect on Cancer Risk
Increased risk for certain cancers can be added to the concerns raised by rising rates of overweight and obesity in the United States. In multiple studies, excess weight represents an independent risk factor for cancer incidence and mortality.1-5 In practice, a body mass index (BMI) ≥25 and <30 kg/m2 defines “overweight” and a BMI ≥30 kg/m2 defines “obesity.”6 The number of overweight and obese individuals in the U.S. has increased consistently over the past 50 years.5 The latest data shows three-quarters of adults and one-third of children are considered overweight or obese, representing substantial increases since the late 1980s.5-7 In particular, the prevalence of excess weight among young people raises concerns about future trends in chronic disease, including cancer.
The World Health Organization has stated that excess weight is second only to tobacco as a known avoidable cause of cancer.8 Since 1992, the rates of most cancers associated with excess weight have increased.5 Surveillance, Epidemiology, and End Results (SEER) data for the United States suggest that each 5-point increase in BMI results in an increased risk of developing cancer that ranges from 13% to 60% depending on cancer type (see Figure 1).5 In 2007, 4% of new cancer cases in men and 7.5% in women were due to obesity, more than 80,000 cases in all.9
How does excess weight influence cancer risk?
Obesity's effect on cancer risk is thought to arise from a complex, interrelated set of mechanisms that vary depending on the cancer type, and include weight-associated changes in the synthesis and action of sex hormones, insulin and insulin-like growth factor (IGF-1), and other cellular growth factors such as AMP-activated kinases.4,5,10-13 In particular, insulin/IGF-1 dysregulation, with its widespread downstream signaling effects, and obesity-related increases in the activity of mammalian target of rapamycin (mTOR), which is central to regulation of multiple cellular signaling pathways, are likely to contribute to increased risk for multiple cancer types.10,13,14
Excess estrogen produced in fatty tissue has been linked to postmenopausal breast cancer and endometrial cancer.6,15,16 Obese women also have higher circulating androgen levels, which combined with higher circulating estrogen levels may increase breast cancer risk.13 Increased levels of insulin and IGF-1 have been associated with tumor development and growth in breast, colorectal, pancreatic, endometrial, and possibly renal cell cancers.5,17 Overweight and obese individuals also tend to exhibit an imbalance in adipokines, with higher levels of proliferation-promoting leptin and lower levels of antiproliferative adiponectin than are seen in nonobese people.6,10,18 Systemic inflammation, oxidative stress, and altered immune response also have been implicated as causes of cancer.6,13 Unfortunately, while all of these postulated mechanisms are plausible and have evidence in their support, there are still gaps in our knowledge. The complexity of the interactions raises doubt that a definitive model relevant to all cancers can actually be created.14