The role of obesity in oesophageal cancer development

Abstract

Abstract:The incidence of oesophageal adenocarcinoma has increased dramatically in the developed world in the last half century. Over approximately the same period there has been an increase in the prevalence of obesity. Multiple epidemiological studies and metaanalyses have confirmed that obesity, especially abdominal, visceral obesity, is a risk factor for gastro-oesophageal reflux, Barrett's oesophagus and oesophageal adenocarcinoma. Although visceral obesity enhances gastro-oesophageal reflux, the available data also show that visceral obesity increases the risk of Barrett's oesophagus and adenocarcinoma via reflux-independent mechanisms. Several possible mechanisms could link obesity with the risk of oesophageal adenocarcinoma in addition to mechanical effects increasing reflux. These include reduced gastric Helicobacter pylori infection, altered intestinal microbiome, factors related to lifestyle, the metabolic syndrome and associated low-grade inflammation induced by obesity and the secretion of mediators by adipocytes which may directly influence the oesophageal epithelium. Of these adipocyte-derived mediators, increased leptin levels have been independently associated with progression to oesophageal adenocarcinoma and in laboratory studies leptin enhances malignant behaviours in cell lines. Adiponectin is also secreted by adipocytes and levels decline with obesity: decreased serum adiponectin levels are associated with malignant progression in Barrett's oesophagus and experimentally adiponectin exerts anticancer effects in Barrett's cell lines and inhibits growth factor signalling. At present there are no proven chemopreventative interventions that may reduce the incidence of obesity-associated oesophageal cancer: observational studies suggest that the combined use of a statin and aspirin or another cyclo-oxygenase inhibitor is associated with a significantly reduced cancer incidence in patients with Barrett's oesophagus.

Assessing the Potential of Thermal Imaging in Recognition of Breast Cancer

“…Unfortunatly, The risk of getting breast cancer has tripled since the bygone half century with respect to modification of lifestyle and other factors (Long and Beales, 2014). Consequently, it is essential to detect breast cancer beforehand to better administrator this growing lethal menace.…”

Reduced Risk of Barrett’s Esophagus in Statin Users: Case–Control Study and Meta-Analysis

“…Several individual studies (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)27) and 2 systematic reviews (that produced essentially identical results despite slightly different methodologies (16,17)) have reported that statin use, and particularly statin use combined with a cyclo-oxygenase inhibitor, is associated with a reduced incidence of esophageal adenocarcinoma. This has been reported in cohort studies and case-control studies of Barrett's patients and population-based studies compared to population-based controls, although not all studies are in agreement (28).…”

“…The reasons for the upsurge are unclear but increasing gastroesophageal reflux and the increasing prevalence of obesity are likely to be important. (3,4). It is accepted that metaplastic transformation of the esophageal squamous mucosa to intestinaltype mucosa (Barrett's esophagus (BE)) is a premalignant phenotype, although the overall rate of progression is relatively low (probably about 1 in 300 patients per year, or less) (5)(6)(7) and this has allowed the development of surveillance and localised treatment strategies such as radio-frequency ablation as means of preventing the development of EAC (8).…”

Abdominal Obesity and Gastroesophageal Cancer Risk: Systematic Review and Meta-Analysis of Prospective Studies

“…One plausible molecular mechanism for obesity-associated carcinogenesis is that visceral adipose tissue, which is metabolically active, promotes the release of inflammatory cytokines and mediators, including free fatty acids, tumor necrosis factor α (TNFα), leptin, and resistin, inhibits the secretion of adiponectin and ultimately leads to development of insulin resistance [8,9,57]. In obesity, insulin resistance leads to chronic hyperinsulinemia.…”

“…There is mounting evidence that obesity increases the risk of certain types of cancers, including post-menopausal breast cancer, colorectal, endometrial, kidney, and pancreatic cancers [2][3][4][5][6][7]. Obesity may have also contributed to the recent rise in gastric cardia carcinoma and esophageal adenocarcinoma (EAC) incidence over the past decades because the prevalence of obesity has increased dramatically at an accelerating and alarming rate during approximately the same time period [8,9]. According to World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) report from 2016, the association of general obesity, as measured by the body mass index (BMI), with esophageal cancer has been judged convincing by the panel [10], whereas the evidence for an association with GC has remained less conclusive [11].…”