Telomere Shortening in Esophageal Epithelium of Alcoholics: Differences in Terms of ADH-1B and ALDH-2 Genotypes and Chromoendoscopy Findings
Junko Aida, Akira Yokoyama, Naotaka Shimomura, Ken-ichi Nakamura, Naoshi Ishikawa, Steven SS Poon, Mutsunori Fujiwara, Motoji Sawabe, Tomio Arai, Kaiyo Takubo. Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Japan; British Columbia Cancer Research Centre, Vancouver, Canada; Japanese Red Cross Medical Center, Tokyo, Japan; Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
Background: Telomeres are repetitive G-rich DNA sequences and associated binding proteins found at the ends of eukaryotic chromosomes, and appear to play a key role in preventing genomic instability. Progressive telomere shortening with age or chronic inflammation may lead to genomic instability during the early stage of carcinogenesis. Squamous cell carcinoma of the esophagus is very rare in the young, but occurs frequently in alcoholics. It is known that the genotypes of ALDH-2 and ADH-1B are involved in carcinogenesis.
Design: All tissues were examined histopathologically. Using our Q-FISH measurement technique, we estimated telomere lengths of epithelial basal cells from 53 alcoholics and 20 age-matched normal controls. Biopsy specimens from alcoholics were obtained from areas unstained by iodine, but were not histologically distinct from control tissue. We then analyzed telomere lengths among patients grouped according to ADH-1B and ALDH-2 genotypes, and also examined the relationship between telomere length and chromoendoscopy findings.
Results: There was no histologic evidence of chronic inflammation in either alcoholics or non-alcoholics. Telomeres in basal cells were significantly shorter in alcoholics than in the controls. However, telomere lengths did not differ among patients grouped by genotype. Telomere lengths in biopsy specimens from unstained areas exceeding 10 mm in diameter (p = 0.0157), or those taken from cases showing multiple unstained areas (p = 0.0402), were significantly shorter than in other cases.
Conclusions: Telomeres in the esophageal epithelium appear to be shorter in alcoholics than in non-alcoholics, suggesting that telomere shortening may be associated with the frequent occurrence of squamous cell carcinoma in alcoholics. It is suggested that alcohol reduces telomere length, irrespective of genotype. Chromoendoscopy appears be provide evidence of telomere shortening in the esophageal epithelium of alcoholics, and may be predictive of carcinogenesis.
Monday, March 19, 2012 1:00 PM
Poster Session II # 86, Monday Afternoon