Revisit of Field Cancerization in Squamous Cell Carcinoma of Upper Aerodigestive Tract: Better Risk Assessment with Epigenetic Markers
Open Access
- 1 December 2011
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Prevention Research
- Vol. 4 (12), 1982-1992
- https://doi.org/10.1158/1940-6207.capr-11-0096
Abstract
We quantified field cancerization of squamous cell carcinoma in the upper aerodigestive tract with epigenetic markers and evaluated their performance for risk assessment. Methylation levels were analyzed by quantitative methylation-specific PCR of biopsied specimens from a training set of 255 patients and a validation set of 224 patients. We also measured traditional risk factors based on demographics, lifestyle, serology, genetic polymorphisms, and endoscopy. The methylation levels of four markers increased stepwise, with the lowest levels in normal esophageal mucosae from healthy subjects without carcinogen exposure, then normal mucosae from healthy subjects with carcinogen exposure, then normal mucosae from cancer patients, and the highest levels were in cancerous mucosae (P < 0.05). Cumulative exposure to alcohol increased methylation of homeobox A9 in normal mucosae (P < 0.01). Drinkers had higher methylation of ubiquitin carboxyl-terminal esterase L1 and metallothionein 1M (P < 0.05), and users of betel quid had higher methylation of homeobox A9 (P = 0.01). Smokers had increased methylation of all four markers (P < 0.05). Traditional risk factors allowed us to discriminate between patients with and without cancers with 74% sensitivity (95% CI: 67%–81%), 74% specificity (66%–82%), and 80% area under the curve (67%–91%); epigenetic markers in normal esophageal mucosa had values of 74% (69%–79%), 75% (67%–83%), and 83% (79%–87%); and both together had values of 82% (76%–88%), 81% (74%–88%), and 91% (88%–94%). Epigenetic markers done well in the validation set with 80% area under the curve (73%–85%). We concluded that epigenetics could improve the accuracies of risk assessment. Cancer Prev Res; 4(12); 1982–92. ©2011 AACR.Keywords
Other Versions
This publication has 45 references indexed in Scilit:
- Linking Epidemiology to Epigenomics—Where Are We Today?Cancer Prevention Research, 2010
- Association between Folate Levels and CpG Island Hypermethylation in Normal Colorectal MucosaCancer Prevention Research, 2010
- Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk allelesGut, 2010
- Relation between normal rectal methylation, smoking status, and the presence or absence of colorectal adenomasCancer, 2010
- No role for human papillomavirus in esophageal squamous cell carcinoma in ChinaInternational Journal of Cancer, 2010
- Early Detection of Superficial Squamous Cell Carcinoma in the Head and Neck Region and Esophagus by Narrow Band Imaging: A Multicenter Randomized Controlled TrialJournal of Clinical Oncology, 2010
- Development of a Novel Output Value for Quantitative Assessment in Methylated DNA Immunoprecipitation-CpG Island Microarray AnalysisDNA Research, 2009
- Promoter Methylation in Cytology Specimens as an Early Detection Marker for Esophageal Squamous Dysplasia and Early Esophageal Squamous Cell CarcinomaCancer Prevention Research, 2008
- DNA methylation: a marker for carcinogen exposure and cancer riskEnvironmental Health and Preventive Medicine, 2007
- Oesophageal squamous cell carcinoma may develop within a background of accumulating DNA methylation in normal and dysplastic mucosaGut, 2007