Mechanisms linking obesity and gastrointestinal cancers
DOI:
https://doi.org/10.12775/JEHS.2020.10.08.041Keywords
obesity, gastrointestinal cancers, mechanisms of carcinogenesis.Abstract
Introduction and purpose: The worldwide prevalence of obesity increased threefold between 1975 and 2016. Obesity is a risk factor for gastrointestinal cancers, including the pancreas, liver, esophagus, colorectum, stomach cardia, and gallbladder. This work is an analysis of the available PubMed literature on relationship between obesity and gastrointestinal cancers and possible mechanisms linking them.
Brief description of the state of knowledge: There is a number of mechanisms responsible for obesity associated gastrointestinal cancers. Excess adiposity leads to: metabolic syndrome, chronic inflammation, altered production of steroid hormones and adipokines as well as changes in insulin and IGF1 signaling. This study examines the processes leading to obesity-associated colorectal, esophageal, gastric, and pancreatic cancers, which are known to be the most prevalent and lethal cancers worldwide. In this review, the mechanisms of gastrointestinal cancerogenesis such as changes in insulin and insulin-like growth factor signaling pathways, chronic inflammation associated to obesity, altered adipokine and inflammatory factors levels, are being discussed.
Conclusions: Thorough understanding of the biological processes connecting obesity, metabolic health and gastrointestinal cancers may help to discover new risk factors and biomarkers, improve preventive strategies and invent ground-breaking treatment.
Key words: obesity; gastrointestinal cancers; mechanisms of carcinogenesis.
References
Organization WH. Obesity and overweight. 2017. http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 20 Nov 2018.
NHLBI. 2013. Managing Overweight and Obesity in Adults: Systematic Evidence Review from the Obesity Expert Panel
Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults
Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body fatness and cancer–viewpoint of the IARC Working Group. N Engl J Med. 2016;375:794–798.
WCRF-AICR. Diet, nutrition, physical activity and colorectal cancer. Continuous Update Project. 2017. http://www.wcrf.org/sites/default/files/CUP%20Colorectal%20Report_2017_Digital.pdf. Accessed 20 Nov 2018.
WCRF-AICR. Diet, nutrition, physical activity and liver cancer. Continuous Update Project. 2015.
http://www.wcrf.org/sites/default/files/Liver-Cancer-2015-Report.pdf. Accessed 20 Nov 2018.
WCRF-AICR. Diet, nutrition, physical activity and oesophageal cancer. Continuous Update Project. 2016.
http://www.wcrf.org/sites/default/files/Oesophageal-cancer-report.pdf. Accessed 20 Nov 2018.
WCRF-AICR. Food, nutrition, physical activity, and the prevention of pancreatic cancer. Continuous Update Project. 2012. http://www.wcrf.org/sites/default/files/Pancreatic-Cancer-2012-Report.pdf. Accessed 20 Nov 2018.
WCRF-AICR. Diet, nutrition, physical activity and stomach cancer. Continuous Update Project. 2016.
http://www.wcrf.org/sites/default/files/Stomach-Cancer-2016-Report.pdf. Accessed 20 Nov 2018.
WCRF-AICR. Diet, nutrition, physical activity and gallbladder cancer. Continuous Update Project. 2015. http://www.wcrf.org/sites/default/files/Gallbladder-Cancer-2015-Report.pdf. Accessed 20 Nov 2018.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018
Feuerer M, Herrero L, Cipolletta D, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15:930–9.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
Crusz SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol. 2015;12:584–596.
Himbert C, Delphan M, Scherer D, Bowers LW, Hursting S, Ulrich CM. Signals from the adipose microenvironment and the obesity-cancer link—a systematic review. Cancer Prev Res. 2017;10:494–506.
Lakka HM, Salonen JT, Tuomilehto J, et al. Obesity and weight gain are associated with increased incidence of hyperinsulinemia in non-diabetic men. Horm Metab Res. 2002;34:492–8.
Tran TT, Naigamwalla D, Oprescu AI, et al. Hyperinsulinemia, but not other factors associated with insulin resistance, acutely enhances colorectal epithelial proliferation in vivo. Endocrinology. 2006;147:1830–1837.
Brick DJ, Gerweck AV, Meenaghan E, et al. Determinants of IGF1 and GH across the weight spectrum: from anorexia nervosa to obesity. European journal of endocrinology / European Federation of Endocrine Societies. 2010;163:185–91.
Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Giovannucci E. Am J Clin Nutr. 2007 Sep; 86(3):s836-42.
Margetic S, Gazzola C, Pegg GG, et al. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord. 2002;26:1407–33
Leptin and cancer. Garofalo C, Surmacz E J Cell Physiol. 2006 Apr; 207(1):12-22.
Motoshima H, Wu X, Sinha MK, et al. Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone. J Clin Endocrinol Metab. 2002;87:5662–7.
Pugeat M, Crave JC, Elmidani M, et al. Pathophysiology of sex hormone binding globulin (SHBG): relation to insulin. J Steroid Biochem Mol Biol. 1991;40:841–849.
Castaner O, Goday A, Park YM, et al. The gut microbiome profile in obesity: a systematic review. Int J Endocrinol. 2018;.
https://doi.org/10.1155/2018/4095789. (ahead of print).
Musso G, Gambino R, Cassader M. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu Rev Med. 2011;62:361–80.
A. Kubo, D.A. Corley. Body mass index and adenocarcinomas of the esophagus or gastric cardia: a systematic review and meta-analysis; Cancer Epidemiol Biomarkers Prev, 15 (2006), pp. 872-878
M. Solaymani-Dodaran, R.F. Logan, J. West, T. Card, C. Coupland Risk of oesophageal cancer in Barrett's oesophagus and gastro-oesophageal reflux Gut, 53 (2004), pp. 1070-1074
Body mass index and adenocarcinomas of the esophagus or gastric cardia: a systematic review and meta-analysis. Kubo A, Corley DA Cancer Epidemiol Biomarkers Prev. 2006 May; 15(5):872-8.
Kai H, Kitadai Y, Kodama M, et al. Involvement of proinflammatory cytokines IL-1beta and IL-6 in progression of human gastric carcinoma. Anticancer Res. 2005;25:709–13.
Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371:569–78.
Stattin P, Bjor O, Ferrari P, et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care. 2007;30:561–7.
Pisani P. Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem. 2008;114:63–70.
Bianchini, F, Kaaks, R, Vainio, H. Overweight, obesity, and cancer risk. Lancet Oncol 2002; 3: 565–574.
Chan, AT, Giovannucci, EL. Primary prevention of colorectal cancer. Gastroenterology 2010; 138: 2029–2043.e10
Guo, YS, Narayan, S, Yallampalli, C. Characterization of insulin like growth factor I receptors in human colon cancer. Gastroenterology 1992; 102: 1101–1108.
Valko, M, Leibfritz, D, Moncol, J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Bio 2007; 39: 44–84.
Adams TD, Stroup AM, Gress RE, et al. Cancer incidence and mortality after gastric bypass surgery. Obesity. 2009;17:796–802
Downloads
Published
How to Cite
Issue
Section
License
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 661
Number of citations: 0
