Ribeiro Pinto Luis Felipe, Teixeira Rossini Ana Maria, Albano Rodolpho Mattos, Felzenszwalb Israel, de Moura Gallo Claudia Victoria, Nunes Rodolfo Acatuassú, Andreollo Nelson Adami
Departamento de Bioqui;mica, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Mutat Res. 2003 Nov;544(2-3):365-73. doi: 10.1016/j.mrrev.2003.06.021.
Esophageal cancer represents one of the most common and lethal cancers around the World. Some areas of South America, including parts of Brazil, present the highest incidence of the disease in the West. The main etiological factors that have been associated with the disease in Brazil are alcohol consumption, tobacco smoking and, in the South, consumption of hot maté. Nitrosamines are the only carcinogens capable of inducing tumors in the esophagus of experimental animals, with the rat being the most susceptible species, mainly due to tissue specific metabolic activation by CYP enzymes. Studies of CYP2A expression in the esophagus of rodents suggest an association between CYP2A expression and esophageal susceptibility to tumor induction. CYP2A6 and CYP2E1, the main enzymes to activate nitrosamines in humans, are the only carcinogen activating CYP enzymes to be expressed in the esophagus of Brazilians. Patients who presented high levels of CYP2A6 expression could activate nitrosamines at rates comparable to the rat. This expression profile is different from those present in French patients. We investigated 34 Brazilian patients regarding the risk associated with polymorphisms in drug metabolizing enzymes and TP53 mutations. A GSTP1 polymorphism presented a clear risk to white and non-white patients to develop esophageal cancer. GSTM1 null polymorphism also seemed to be associated with an increased risk. CYP2A6, CYP2E1, SOD2, and GSTT1 polymorphisms were not associated with an increased risk of esophageal cancer. TP53 mutations occurred mostly in exon 7, differing from the mutation profile found in the IARC database. The preliminary results obtained with polymorphisms of drug metabolizing enzymes and TP53 mutations need to be confirmed in a larger number of samples in order to compare the mechanisms of esophageal cancer development in Brazilians with that of other populations.
食管癌是全球最常见且致命的癌症之一。南美洲的一些地区，包括巴西的部分地区，是西方该疾病发病率最高的地区。在巴西，与该疾病相关的主要病因是饮酒、吸烟，以及在南部地区饮用滚烫的马黛茶。亚硝胺是唯一能够在实验动物食管中诱发肿瘤的致癌物，大鼠是最易受影响的物种，这主要是由于细胞色素P450（CYP）酶的组织特异性代谢激活作用。对啮齿动物食管中CYP2A表达的研究表明，CYP2A表达与食管对肿瘤诱发的易感性之间存在关联。CYP2A6和CYP2E1是人类体内激活亚硝胺的主要酶，也是在巴西人食管中表达的仅有的致癌物激活CYP酶。CYP2A6表达水平高的患者激活亚硝胺的速率与大鼠相当。这种表达谱与法国患者不同。我们调查了34名巴西患者，研究药物代谢酶多态性和TP53突变相关的风险。一种谷胱甘肽S-转移酶P1（GSTP1）多态性对白种人和非白种人患者患食管癌呈现出明显风险。谷胱甘肽S-转移酶M1（GSTM1）无效多态性似乎也与风险增加有关。CYP2A6、CYP2E1、超氧化物歧化酶2（SOD2）和谷胱甘肽S-转移酶T1（GSTT1）多态性与食管癌风险增加无关。TP53突变大多发生在外显子7，与国际癌症研究机构（IARC）数据库中的突变谱不同。药物代谢酶多态性和TP53突变的初步研究结果需要在更多样本中得到证实，以便比较巴西人与其他人群食管癌发生机制的异同。
