The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples

Our plain-English summary of The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples, by P. Grignani, S.D. Visonà, M.V. Fronda, et al (Frontiers in Public Health, 2023).

The study

• Authors: P. Grignani, S.D. Visonà, M.V. Fronda, P. Borrelli, M.C. Monti, B. Bertoglio, A. Conti, P. Fattorini, C. Previderè
• Journal: Frontiers in Public Health
• Published: 2023;11:1236558
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright © 2023 Grignani, Visonà, Fronda, Borrelli, Monti, Bertoglio, Conti, Fattorini and Previderè.

In plain English

This genetic study on archived autopsy tissue examined whether six DNA variants (SNPs) in genes involved in iron handling and the tumor environment were linked to mesothelioma after asbestos exposure. The authors tested heart tissue from 48 men who died of pleural malignant mesothelioma and 48 asbestos-exposed men who died of non-cancer causes. All lived in or near Broni, Italy, where an asbestos-cement plant used chrysotile and crocidolite (with small amounts of amosite) from 1932 to 1993. They also tested 76 healthy men and used data on 107 healthy Tuscan Italians from the 1000 Genomes database. One variant, in the hephaestin gene, showed no variation in any of these four groups, so it was left out of the statistical comparisons. For the other five, the two exposed groups did not differ significantly, except for one transferrin variant. Two copies of its G form appeared in 9 of 48 men with mesothelioma and 2 of 48 without (odds ratio 5.31, 95% CI 1 to 26). The authors said this could not be confirmed given the wide interval. The authors concluded these SNPs do not seem useful markers of mesothelioma susceptibility, contrary to an earlier study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective genetic comparison (case-control type) of DNA from archived autopsy tissue, with healthy controls and a public genetic database for comparison
• Who was studied: 48 men with documented asbestos exposure who died of pleural malignant mesothelioma (MM) and 48 men with documented asbestos exposure who died of other, non-neoplastic causes (NMAE; 33 of them had asbestosis confirmed after death). All had autopsies between 2005 and 2018 and lived in Broni (North-West Italy) or adjacent areas. Comparison groups were 76 healthy men without known asbestos exposure and 107 healthy Tuscan Italians from the 1000 Genomes database.
• Exposure: Occupational exposure at, or residential exposure near, an asbestos-cement plant in Broni that used a mixture of chrysotile and crocidolite with small amounts of amosite from 1932 to 1993. Exposure was occupational in 34 MM and 36 NMAE subjects, and environmental from the plant in 14 MM and 12 NMAE subjects.
• Main results:
  • Between the mesothelioma group and the asbestos-exposed group without mesothelioma, there was no statistically significant difference in allele or genotype frequencies for any marker, except SNP rs2715631 in the transferrin gene under the genotypic model (p = 0.018).
  • For transferrin SNP rs2715631, the GG genotype was found in 9 of 48 (18.75%) mesothelioma subjects, 2 of 48 (4.17%) exposed subjects without mesothelioma, and 7 of 76 (9.21%) healthy controls.
  • Under the recessive model (GG versus TT and TG), the mesothelioma versus exposed non-mesothelioma comparison gave p = 0.025, odds ratio 5.31, 95% CI 1 to 26.
  • The authors stated that this transferrin difference cannot be confirmed because the confidence interval is so wide.
  • The hephaestin SNP rs3747359 was typed and reported but showed no variation in the three study groups or the Tuscan 1000 Genomes subgroup, so it was excluded from the statistical comparisons.
  • There were no statistically significant differences between the mesothelioma group and the healthy controls, or between the exposed non-mesothelioma group and the healthy controls.
• The authors' conclusion: The authors concluded that, in this series, the iron-related SNPs studied do not seem to be useful markers of individual susceptibility to mesothelioma. They noted this disagrees with previous literature (Crovella et al.).
• Limitations the authors state:
  • The wide confidence interval may be due to the limited number of subjects in the two exposed groups.
  • The archived autopsy samples were sometimes hard to retrieve, and good-quality DNA was sometimes difficult to obtain from them.
  • The genotyping methods differed from those of the earlier study the authors compared against. DNA degradation and modification could also explain some of the differences.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Asbestos Exposure, Malignant Mesothelioma, Prognosis, Pleura, Pericardium, Peritoneum, Asbestos Bodies.

Related studies

• Commentary: The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples — G. Tagarakis, F. Tsolaki, et al. (2024)
• Is a single nucleotide polymorphism a risk factor for lung cancer in the matrix metalloproteinase-2 promoter? — B. Ayşegül, G.H. Veysi, et al. (2011)
• Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples — S.D. Visonà, S. Capella, et al. (2021)
• Iron homeostasis in the lung following asbestos exposure — A.J. Ghio, J. Stonehuerner, et al. (2008)
• The biological effect of asbestos exposure is dependent on changes in iron homeostasis — A.J. Ghio, J.M. Soukup, et al. (2016)
• Disruption of iron homeostasis in mesothelial cells after talc pleurodesis — A.J. Ghio, J.M. Soukup, et al. (2012)

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