Abstract:
Asbestos-related diseases still represent a major public health problem all over the world. Among them, malignant mesothelioma (MM) is a poor-prognosis cancer, arising from the serosal lining of the pleura, pericardium and peritoneum, triggered by asbestos exposure. Literature data suggest the key role of iron metabolism in the coating process leading to the formation of asbestos bodies, considered to be both protective and harmful. Two sample sets of individuals were taken into consideration, both residing in Broni or neighboring cities (Northwestern Italy) where an asbestos cement factory was active between 1932 and 1993. The present study aims to compare the frequency of six SNPs involved in iron trafficking, previously found to be related to protection/predisposition to MM after asbestos exposure, between 48 male subjects with documented asbestos exposure who died of MM and 48 male subjects who were exposed to asbestos but did not develop MM or other neoplastic respiratory diseases (Non-Mesothelioma Asbestos Exposed - NMAE). The same analysis was performed on 76 healthy male controls. The allelic and genotypic frequencies of a sub-group of 107 healthy Italian individuals contained in the 1000 genomes database were considered for comparison. PCR-multiplex amplification followed by SNaPshot mini-sequencing reaction was used. The findings presented in this study show that the allelic and genotypic frequencies for six SNP markers involved in iron metabolism/homeostasis and the modulation of tumor microenvironment are not significantly different between the two sample sets of MM and NMAE. Therefore, the SNPs here considered do not seem to be useful markers for individual susceptibility to mesothelioma. This finding is not in agreement with previous literature.
摘要:
与石棉有关的疾病仍然是全世界的主要公共卫生问题。其中,恶性间皮瘤(MM)是一种预后不良的癌症,从胸膜的浆膜衬里,心包和腹膜,石棉暴露引发的。文献数据表明,铁代谢在涂层过程中的关键作用导致石棉体的形成,被认为是保护和有害的。考虑了两组个体样本,都居住在布罗尼或邻近城市(意大利西北部),那里的石棉水泥厂在1932年至1993年之间活跃。本研究旨在比较参与铁贩运的六个SNP的频率,先前发现与石棉暴露后对MM的保护/易感性有关,有记录的石棉暴露的48名男性受试者死于MM和48名男性受试者暴露于石棉但未发展为MM或其他肿瘤性呼吸道疾病(非间皮瘤石棉暴露-NMAE)。对76名健康男性对照进行相同的分析。考虑比较1000个基因组数据库中包含的107个健康意大利个体的亚组的等位基因和基因型频率。使用PCR-多重扩增,然后进行SNaPshot微型测序反应。这项研究中提出的发现表明,涉及铁代谢/体内平衡和肿瘤微环境调节的六个SNP标记的等位基因和基因型频率在MM和NMAE的两个样品集之间没有显着差异。因此,此处考虑的SNP似乎不是个体对间皮瘤易感性的有用标志物.这一发现与以前的文献不一致。