Possible Mechanisms: Hyperinsulinemia and Endocrine Disrupting Chemicals
Nonalcoholic fatty liver disease is present in patients with obesity and type 2 diabetes mellitus (1). Concomitant hyperinsulinemia in such patients can promote tumor growth via the insulin receptor and activation of the mitogenic signaling pathways PI13-AKT-mTOR and RAS-MAPK. Furthermore, hypercholesterolemia which is often present in these patient groups can trigger tumor growth and development of metastases (2). Endocrine disrupting chemicals/EDCs (for instance, plastics such as bisphenol A, industrial solvents and lubricants such as polychlorinated biphenyles, pesticides, herbicides, and others) also can contribute to tumor induction. Many of these EDCs are lipophilic and remain stored in fatty tissue exerting mutagenic effects via epigenetic mechanisms such as DNA methylation changes (3). This way dichlorodiphenyltrichloroethane can cause breast cancer and testicular cancer and methyl bromide, a fungicide, as well as organochlorine and organophosphate pesticides can trigger prostate cancer. The main risk factor for skin cancer is ultraviolet radiation. However, besides nonalcoholic fatty liver disease and genetic predisposition EDCs are also a risk factor (4). After reviewing multiple epidemiological studies, the International Agency for Research on Cancer concluded that there is sufficient evidence to prevent many cancers (esophagus, gastric cardia, colon, rectum, liver, gallbladder, pancreas, breast, uterus, and others) by avoiding being overweight or obese. Acknowledging the current high prevalence of obesity of approx. 24 percent of adults and increasingly also amongst children and adolescents in Germany (with even higher prevalence rates in the United States of America), timely and good cancer prevention is recommended, as suggested by the authors (1). Moreover, patients should be examined for the possible presence of nonalcoholic fatty liver disease and existing hyperinsulinemia in such patients should be optimally treated.
Prof. Dr. med. Christian A. Koch, FACP, MACE
Assistant Prof. Dr. med. Michael J. Bartel
Prof. David S. Weinberg, MD, MSc
Department of Medicine, Fox Chase Cancer Center
Conflict of interest statement
The authors declare that no conflict of interest exists.
|1.||Huber Y, Labenz C, Michel M, et al.: Tumor incidence in patients with non-alcoholic fatty liver disease. Dtsch Arztebl Int 2020; 117: 719–24 VOLLTEXT|
|2.||Gallagher EJ, LeRoith D: Hyperinsulinaemia in cancer. Nat Rev Cancer 2020; 20: 629–44 CrossRef MEDLINE|
|3.||Koch CA, Diamanti-Kandarakis E: Introduction to endocrine disrupting chemicals: is it time to act? Rev Endocr Metab Disord 2015; 16: 269–70 CrossRef MEDLINE|
|4.||Karimi K, Lindgren TH, Koch CA, Brodell RT: Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer. Rev Endocr Metab Disord 2016; 17: 389–403 CrossRef MEDLINE|