与铁稳态相关的单核苷酸多态性在石棉暴露后间皮瘤易感性中的作用:对自动光学样本的遗传研究。
The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples.
发表日期:2023
作者:
Pierangela Grignani, Silvia Damiana Visonà, Maria Vittoria Fronda, Paola Borrelli, Maria Cristina Monti, Barbara Bertoglio, Adelaide Conti, Paolo Fattorini, Carlo Previderè
来源:
FRONTIERS IN PUBLIC HEALTH
摘要:
与石棉相关的疾病仍然是全世界的一个主要公共卫生问题。其中,恶性间皮瘤(MM)是一种预后不良的癌症,起源于胸膜、心包和腹膜的浆膜层,由石棉暴露引发。文献数据表明,铁代谢在导致石棉体形成的涂层过程中发挥着关键作用,石棉体被认为既具有保护作用,又有害。考虑了两组个人样本,均居住在布罗尼或邻近城市(意大利西北部),那里有一家石棉水泥厂在 1932 年至 1993 年间活跃。本研究旨在比较之前参与铁贩运的 6 个 SNP 的频率。发现与石棉暴露后对 MM 的保护/易感性相关,研究对象为 48 名有记录的石棉暴露且死于 MM 的男性受试者和 48 名暴露于石棉但未患 MM 或其他肿瘤性呼吸道疾病(非间皮瘤石棉)的男性受试者暴露-NMAE)。对 76 名健康男性对照进行了相同的分析。考虑对 1000 个基因组数据库中包含的 107 名健康意大利个体的亚组的等位基因和基因型频率进行比较。使用 PCR 多重扩增,然后进行 SNaPshot 小型测序反应。本研究的结果表明,涉及铁代谢/稳态和肿瘤微环境调节的 6 个 SNP 标记的等位基因和基因型频率在 MM 和 NMAE 的两个样本组之间没有显着差异。因此,这里考虑的 SNP 似乎并不是个体对间皮瘤易感性的有用标记。这一发现与之前的文献不一致。版权所有 © 2023 Grignani、Visonà、Fronda、Borrelli、Monti、Bertoglio、Conti、Fattorini 和 Previderè。
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.Copyright © 2023 Grignani, Visonà, Fronda, Borrelli, Monti, Bertoglio, Conti, Fattorini and Previderè.