Urologic cancers (UC) account for 13.1% of all new
cancer cases and 7.9% of all
cancer-related deaths. A growing body of evidence has indicated a potential causal link between
obesity and UC. The aim of the present review is to appraise in a critical and integrative manner evidence from meta-analyses and mechanistic studies on the role of
obesity in four prevalent UC (kidney-KC, prostate-PC, urinary bladder-UBC, and
testicular cancer-TC). Special emphasis is given on Mendelian Randomization Studies (MRS) corroborating a genetic causal association between
obesity and UC, as well as on the role of classical and novel
adipocytokines. Furthermore, the molecular pathways that link
obesity to the development and progression of these
cancers are reviewed. Available evidence indicates that
obesity confers increased risk for KC, UBC, and advanced PC (20-82%, 10-19%, and 6-14%, respectively), whereas for TC adult height (5-cm increase) may increase the risk by 13%. Obese females tend to be more susceptible to UBC and KC than obese males. MRS have shown that a higher genetic-predicted BMI may be causally linked to KC and UBC but not PC and TC. Biological mechanisms that are involved in the association between excess
body weight and UC include the
Insulin-like Growth Factor axis, altered availability of
sex hormones, chronic
inflammation and oxidative stress, abnormal secretion of
adipocytokines, ectopic fat deposition,
dysbiosis of the gastrointestinal and urinary tract microbiomes and circadian rhythm dysregulation. Anti-hyperglycemic and non-steroidal anti-inflammatory drugs,
statins, and
adipokine receptor agonists/antagonists show potential as adjuvant
cancer therapies. Identifying
obesity as a modifiable risk factor for UC may have significant public health implications, allowing clinicians to tailor individualized prevention strategies for patients with excess
body weight.