Bariatric surgery in the prevention of obesity-associated cancers: mechanistic implications

Obesity is associated with an increased risk of at least 13 different cancers, as well as worse cancer outcomes and increased cancer mortality. As rates continue to rise both in the United States and worldwide, obesity is poised to become the leading lifestyle-related risk factor for cancer. Currently, the most effective treatment for patients with severe obesity is bariatric surgery. Multiple cohort studies have demonstrated a consistent >30% decreased risk of cancer incidence in women, but not men, following bariatric surgery. However, the physiologic mechanisms driving obesity-associated cancer and the cancer-protective effect of bariatric surgery are not clearly defined. In this review, we highlight emerging concepts in the mechanistic understanding of obesity-associated cancer. Evidence from both human studies and preclinical animal models suggest that obesity drives carcinogenesis through dysregulation of systemic metabolism, immune dysfunction, and an altered gut microbiome. Additionally, we present related findings to suggest that bariatric surgery may disrupt and even reverse many of these mechanisms. Finally, we discuss the use of preclinical bariatric surgery animal models in the study of cancer biology. The prevention of cancer is emerging as an important indication for bariatric surgery. Elucidating the mechanisms through which bariatric surgery limits carcinogenesis is critical to developing a variety of interventions that intercept obesity-driven cancer.