Obesity and main urologic cancers: Current systematic evidence, novel biological mechanisms, perspectives and challenges. (June 2023)

• Record Type: Journal Article
• Authors: Papavasileiou, Georgios; Tsilingiris, Dimitrios; Spyrou, Nikolaos; Vallianou, Natalia G.; Karampela, Irene; Magkos, Faidon; Dalamaga, Maria
• Is Part Of: Seminars in cancer biology. Volume 91(2023)
• Page Start: 70
• Page End: 98
• Publication Date: 2023-06
• Subjects: AMPK Adenosine monophosphate-activated protein kinase -- AR Androgen Receptor -- BCR Biochemical Cancer Recurrence -- BMI Body Mass Index -- CI Confidence Interval -- CVD Cardiovascular Disease -- E2 Estradiol-2 -- ERK Extracellular signal-Regulated Kinase -- GST Glutathione-S-transferase -- GSK3 Glycogen Synthase Kinase 3 beta -- HR Hazard Ratio -- IGF Insulin-like Growth factor -- IGFBP Insulin-like Growth Factor Binding Proteins -- IR Insulin Resistance -- JAK Janus-Kinase -- KC Kidney Cancer -- LKB1 Liver Kinase-B1 -- MAPK Mitogen-Activated Protein Kinase -- MIC-1 Macrophage-inhibiting cytokine-1 -- MMP Matrix Metalloproteinases Protein -- MRS Mendelian Randomization Study -- MetS Metabolic Syndrome -- NOS Nitric Oxide Synthase -- NSAIDs Non-Steroidal Anti-inflammatory Drugs -- NOX NADPH oxidase enzymes -- Nrf2 Nuclear factor erythroid 2-related factor 2 -- OR Odds Ratio -- PA Physical Activity -- PI3K Phosphoinositide 3-kinase -- PC Prostate Cancer -- PKB Protein-Kinase-B -- PPARγ Peroxisome Proliferator-activated Receptor-γ -- PSA Prostate Specific Antigen -- RAS Reticular Activated System -- RAF Rapidly Accelerated Fibrosarcoma -- RCC Renal Cell Carcinoma -- RNS Reactive Nitrogen Species -- ROS Reactive Oxygen Species -- RTC Randomized Controlled Trial -- SAT Subcutaneous Adipose Tissue -- SHBG Sex Hormone Binding Globulin -- SHLA Superactive Human Leptin Antagonist -- SMD Standard Mean Difference -- SR Systematic Review -- TC Testicular Cancer -- TNF-α Tumor Necrosis Factor-α -- T2DM Type 2 Diabetes Mellitus -- UBC Urinary Bladder Cancer -- UC Urinary Cancer -- VAI Visceral Adipose Index -- VAT Visceral Adipose Tissue -- VD Vitamin D -- WAT White Adipose Tissue -- WCRF/AICR World Cancer Research Fund/American Institute for Cancer Research -- WC Waist Circumference -- WHO World Health Organization -- WHR Waist-to-Hip Ratio; Bladder cancer -- Obesity -- Prostate cancer -- Renal cancer -- Testicular cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2023.03.002
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: 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.