The obesity paradox in lung cancer: is there a missing biological link?

Obesity is a well-established risk factor for cardiovascular diseases (1) and type II diabetes (2). It has also been long associated with increased risk and mortality of most cancer types (3). Paradoxically, high body mass index (BMI) has been linked with both a reduced risk of lung cancer and better overall outcome of lung cancer patients. The mechanism for the paradoxical benefit of obesity observed consistently in multiple cohort studies, termed as the “obesity paradox”, remains unclear. The hypotheses of a confounding effect by smoking or reverse causation due to cancer-associated weight loss have been already considered as possible reasonable interpretations, but have failed to explain the lung cancer obesity paradox in its entirety (4,5).