Epigenetics in Obesity and Esophageal Cancer
Barrett’s esophagus (BE) is a metaplastic condition that is believed to develop in the esophagus due to chronic acid reflux and can progress to esophageal adenocarcinoma (EAC). Obesity, a well-known risk factor for BE and EAC, may increase the risk for BE
- PDF / 289,951 Bytes
- 19 Pages / 439.37 x 666.14 pts Page_size
- 57 Downloads / 222 Views
Epigenetics in Obesity and Esophageal Cancer Andrew M. Kaz and William M. Grady
Abstract Barrett’s esophagus (BE) is a metaplastic condition that is believed to develop in the esophagus due to chronic acid reflux and can progress to esophageal adenocarcinoma (EAC). Obesity, a well-known risk factor for BE and EAC, may increase the risk for BE/EAC indirectly by increasing the frequency of gastroesophageal reflux and directly through obesity-mediated inflammation and the secretion of cancer-promoting molecules by adipocytes. Epigenetic alterations, which are commonly seen in BE and EAC, have been associated with chronic inflammation in the esophagus and also with obesity in other tissues. There is emerging evidence that elevated BMI is associated with the altered DNA methylation observed in BE, dysplastic BE, and EAC tissues. There is also some suggestion that genes involved in cancer-related pathways and pathways implicated in obesityrelated cancers and adipose-mediated inflammation (insulin, IGF-1) demonstrate altered methylation in obese individuals. Thus, obesity appears to influence the formation and progression of BE to EAC via epigenetic mechanisms. Keywords Barrett’s esophagus • Esophageal adenocarcinoma • DNA methylation • Obesity • Gastro esophageal reflux disease
Abbreviations BE EAC LGD HGD
Barrett’s esophagus Esophageal adenocarcinoma Low-grade dysplasia High-grade dysplasia
A.M. Kaz (*) VA Puget Sound Health Care System, 1660 S. Columbian Way, S-111-Gastro, Seattle, WA 98108, USA e-mail: [email protected] W.M. Grady Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, D4-100, Seattle, WA 98109, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 N.A. Berger (ed.), Epigenetics, Energy Balance, and Cancer, Energy Balance and Cancer 11, DOI 10.1007/978-3-319-41610-6_8
191
192
SQ FFPE HM450 UTR DML DMR BMI NCI-PID KEGG GO
A.M. Kaz and W.M. Grady
Squamous esophagus Formalin-fixed paraffin-embedded HumanMethylation450 Untranslated region Differentially methylated loci/locus Differentially methylated region Body mass index National Cancer Institute Pathway Interaction Database Kyoto Encyclopedia of Genes and Genomes Gene ontology
Introduction Esophageal adenocarcinoma (EAC) is thought to develop from a pre-cancerous condition of the esophagus called Barrett’s esophagus (BE). BE is a metaplastic condition where specialized intestinal columnar epithelium replaces the normal squamous epithelium in the esophagus [76]. BE is suspected when a salmon pink-colored mucosal lining is visualized in the tubular esophagus during an endoscopic examination and is confirmed by histopathological evaluation demonstrating intestinaltype epithelium in biopsies obtained proximal to the gastro-esophageal junction (GEJ) [78]. Clinically, BE is important because it is recognized as the precursor to esophageal adenocarcinoma (EAC); although the absolute risk of BE progression is low (approximately 0.2 %/year), individuals with BE have an approximately 25× increased risk of developing E
Data Loading...
