OA: Obesity and Cancer: Insights for Clinicians: JCO

Open access

 The obesity epidemic is now three decades old. During that time, there has been an overall increase in incidence of both male and female cancer in the United States, related mainly to the smoking-associated epidemic of lung cancer. However, there is no clear evidence that obesity has led to a substantial increase in cancer incidence or negatively affected cancer outcomes in the United States over this period (Figs 2 and 3).²¹ For example, incidence of endometrial and colorectal cancer, both obesity associated, have not increased in women, and colorectal cancer incidence in men has fallen. This lack of concordance between population trends in obesity versus cancer incidence and outcome may reflect a noncausal relationship.

Three articles delve into potential biologic mechanisms underlying the obesity-cancer association. These articles address mechanisms from different perspectives, recognizing that obesity is associated with a broad range of interrelated changes in adipose tissue, systemic physiology, and cellular metabolism, and it is likely that multiple mechanisms contribute simultaneously to the obesity-cancer association, with different mechanisms having different relative contributions in different settings.

 Lohmann et al¹⁵ discuss the contribution of obesity-associated systemic physiology to the obesity-cancer link. They review insulin resistance, discussing molecular mechanisms that stimulate the growth of cancer cells as well as observational evidence linking insulin resistance to increased cancer risk and poor cancer outcomes. Two obesity-associated adipokines (leptin and adiponectin) seem to have differing associations with cancer, leptin being potentially associated with increased risk and worse prognosis and adiponectin having opposite associations. Finally, potential contributions of reproductive hormones to female cancers (breast, gynecologic) are discussed. Therapeutic options for reversing some of the physiologic changes potentially implicated in the obesity-cancer link are also reviewed.