title: Obesity and cancer: mechanistic insights from transdisciplinary studies.
abstract: Obesity is associated with a range of health outcomes that are of clinical and public health significance, including cancer. Herein, we summarize epidemiologic and preclinical evidence for an association between obesity and increased risk of breast and prostate cancer incidence and mortality. Moreover, we describe data from observational studies of weight change in humans and from calorie-restriction studies in mouse models that support a potential role for weight loss in counteracting tumor-promoting properties of obesity in breast and prostate cancers. Given that weight loss is challenging to achieve and maintain, we also consider evidence linking treatments for obesity-associated co-morbidities, including metformin, statins and non-steroidal anti-inflammatory drugs, with reduced breast and prostate cancer incidence and mortality. Finally, we highlight several challenges that should be considered when conducting epidemiologic and preclinical research in the area of obesity and cancer, including the measurement of obesity in population-based studies, the timing of obesity and weight change in relation to tumor latency and cancer diagnosis, and the heterogeneous nature of obesity and its associated co-morbidities. Given that obesity is a complex trait, comprised of behavioral, epidemiologic and molecular/metabolic factors, we argue that a transdisciplinary approach is the key to understanding the mechanisms linking obesity and cancer. As such, this review highlights the critical need to integrate evidence from both epidemiologic and preclinical studies to gain insight into both biologic and non-biologic mechanisms contributing to the obesity-cancer link.
authors.affiliation: Department of EpidemiologyCB 7435, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USALineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USADepartment of NutritionUniversity of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USA Department of EpidemiologyCB 7435, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USALineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USADepartment of NutritionUniversity of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USA allott@email.unc.edu.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Allott
authors.affiliation: Department of EpidemiologyCB 7435, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USALineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USADepartment of NutritionUniversity of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USA Department of EpidemiologyCB 7435, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USALineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USADepartment of NutritionUniversity of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, North Carolina 27599, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hursting
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology; D031204:Caloric Restriction; D015984:Causality; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D055088:Early Detection of Cancer; D005260:Female; D012739:Gonadal Steroid Hormones; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000453:epidemiology; D015994:Incidence; D008019:Life Style; D008297:Male; D008593:Menopause; D008687:Metformin / Q000627:therapeutic use; D051379:Mice; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D009376:Neoplasms, Hormone-Dependent / Q000453:epidemiology / Q000209:etiology; D009765:Obesity / Q000188:drug therapy / Q000453:epidemiology* / Q000503:physiopathology / Q000628:therapy; D064887:Observational Studies as Topic; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000209:etiology; D012306:Risk; D015431:Weight Loss
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D012739:Gonadal Steroid Hormones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008687:Metformin
keywords: NSAIDs; aspirin; breast cancer; cholesterol; epidemiology; insulin; mechanisms; metformin; mouse models; obesity; prostate cancer; screening; statins; transdisciplinary; weight loss