Junko Aida1, Akira Yokoyama2, Sachiko Hara3, Tatsuro Ishizaki4, Mutsunori Fujiwara5, Tomio Arai6, Toshiyuki Ishiwata1, Kaiyo Takubo1. 1. Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. 2. Clinical Research Unit, National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan. 3. Department of Laboratory Medicine, National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan. 4. Human Care Research Team, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. 5. Department of Clinical Medicine, Japanese Red Cross Medical Center, Tokyo, Japan. 6. Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
Abstract
BACKGROUND: Progressive telomere shortening with age or chronic inflammation may lead to genomic instability that characterizes the early stage of carcinogenesis. Certain risk factors, such as drinking alcoholic beverages or smoking, predispose the oral mucosa to squamous cell carcinoma. The ADH1B and ALDH2 genotypes can influence the risk of cancer due to alcohol drinking. In the present study, we analyzed chromosomal instability due to telomere shortening in the oral mucosa in relation to cancer risk factors. DESIGN: Using our quantitative fluorescence in situ hybridization (Q-FISH) technique, we estimated telomere lengths (TL) in the background mucosa from 23 cases of mucosal carcinoma, 12 cases of oral epithelial dysplasia, and 21 non-neoplasia cases. ALDH2 and ADH1B genotypes were determined using DNA extracted from paraffin sections. We analyzed TL in relation to alcohol drinking, smoking, and cancer multiplicity. RESULTS: Telomeres in the backgrounds of dysplasia and mucosal carcinoma were significantly shorter than in controls. In comparison with adult controls, telomeres were significantly (P = .038) shorter in the ADH1B less-active type (ADH1B*1/*1), but not (P = .841) in the ALDH2 inactive type (ALDH2*1/*2 or *2/*2). Cancer multiplicity and smoking had no significant relationship with TL. CONCLUSION: Telomeres in the oral epithelium are shorter in cases of oral dysplasia or mucosal carcinoma than in non-neoplasia. Unlike the esophageal epithelium of alcoholics, they are also shorter in individuals with the less-active rather than the active ADH1B gene. Telomeres in the oral epithelium may be directly affected by alcohol drinking.
BACKGROUND: Progressive telomere shortening with age or chronic inflammation may lead to genomic instability that characterizes the early stage of carcinogenesis. Certain risk factors, such as drinking alcoholic beverages or smoking, predispose the oral mucosa to squamous cell carcinoma. The ADH1B and ALDH2 genotypes can influence the risk of cancer due to alcohol drinking. In the present study, we analyzed chromosomal instability due to telomere shortening in the oral mucosa in relation to cancer risk factors. DESIGN: Using our quantitative fluorescence in situ hybridization (Q-FISH) technique, we estimated telomere lengths (TL) in the background mucosa from 23 cases of mucosal carcinoma, 12 cases of oral epithelial dysplasia, and 21 non-neoplasia cases. ALDH2 and ADH1B genotypes were determined using DNA extracted from paraffin sections. We analyzed TL in relation to alcohol drinking, smoking, and cancer multiplicity. RESULTS: Telomeres in the backgrounds of dysplasia and mucosal carcinoma were significantly shorter than in controls. In comparison with adult controls, telomeres were significantly (P = .038) shorter in the ADH1B less-active type (ADH1B*1/*1), but not (P = .841) in the ALDH2 inactive type (ALDH2*1/*2 or *2/*2). Cancer multiplicity and smoking had no significant relationship with TL. CONCLUSION: Telomeres in the oral epithelium are shorter in cases of oral dysplasia or mucosal carcinoma than in non-neoplasia. Unlike the esophageal epithelium of alcoholics, they are also shorter in individuals with the less-active rather than the active ADH1B gene. Telomeres in the oral epithelium may be directly affected by alcohol drinking.
Authors: Andrea Maugeri; Martina Barchitta; Roberta Magnano San Lio; Maria Clara La Rosa; Claudia La Mastra; Giuliana Favara; Marco Ferlito; Giuliana Giunta; Marco Panella; Antonio Cianci; Antonella Agodi Journal: Int J Environ Res Public Health Date: 2021-05-10 Impact factor: 3.390