Yokoyama Akira, Omori Tai, Tanaka Yoichi, Yokoyama Tetsuji, Sugiura Hitoshi, Mizukami Takeshi, Matsushita Sachio, Higuchi Susumu, Maruyama Katsuya, Ishii Hiromasa, Hibi Toshifumi
National Hospital Organization Kurihama Alcoholism Center, 5-3-1 Nobi, Yokosuka, Kanagawa 239-0841, Japan.
Cancer Lett. 2007 Mar 18;247(2):243-52. doi: 10.1016/j.canlet.2006.05.004. Epub 2006 Jun 6.
Synchronous multiple intra-esophageal squamous cell carcinomas (SCCs) or oropharyngolaryngeal SCCs are common in alcoholics with esophageal SCC, and more frequently found in those with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2). p53 alterations have been suspected as key molecular events in such multifocal esophageal carcinogenesis. We studied 95 Japanese alcoholic men with Tis and mucosal invasive esophageal SCC and found very high levels of p53 protein accumulation occurring in early esophageal SCC. Synchronous cancer multiplicity in the upper aerodigestive tract was found in 40 patients. p53 expression was not correlated with either cancer multiplicity or ALDH2 genotype. The risk for cancer multiplicity was associated with inactive heterozygous ALDH2 alone (OR=4.22) among the risk factors investigated, which also included smoking, less-active alcohol dehydrogenase-1B, and macrocytosis, enhancing the validity of the link between acetaldehyde exposure and cancer multiplicity.
同步性多原发性食管鳞状细胞癌（SCC）或口咽喉SCC在患有食管SCC的酗酒者中很常见，在携带无活性杂合醛脱氢酶-2（ALDH2）的患者中更常见。p53改变被怀疑是这种多灶性食管癌发生过程中的关键分子事件。我们研究了95名患有Tis和黏膜浸润性食管SCC的日本男性酗酒者，发现早期食管SCC中p53蛋白积累水平非常高。40例患者在上消化道发现同步性癌灶。p53表达与癌灶数量或ALDH2基因型均无相关性。在所研究的风险因素中，包括吸烟、活性较低的乙醇脱氢酶-1B和大细胞性贫血，癌灶数量的风险仅与无活性杂合ALDH2相关（OR = 4.22），这增强了乙醛暴露与癌灶数量之间联系的可信度。
