The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma

Levpuscek, Kristina; Goričar, Katja; Kovač, Viljem; Dolžan, Vita; Franko, Assoc. Prof. Alenka

doi:10.2478/raon-2019-0016

Cited by 7 publications

(11 citation statements)

References 32 publications

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“…DNA samples of all other subjects had been isolated during previous studies. 44 Genotyping was performed using competitive allele-specific PCR (KASP), the KASP Master mix (LGC, Middlesex, UK) and custom KASP Genotyping Assay (LGC, Middlesex, UK) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma

Piber

Vavpetic

Goričar

et al. 2020

Radiology and Oncology

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BackgroundAsbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM.Subjects and methodsIn total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis.ResultsWe found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13–0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14–0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28–0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050).ConclusionsOur findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.

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Section: Methodsmentioning

confidence: 99%

The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma

Piber

Vavpetic

Goričar

et al. 2020

Radiology and Oncology

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“…Recently, a larger number of 273 malignant mesothelioma patients and 193 controls from the same Slovenian cohort were analysed for four SNPs in two DNA repair genes (ERCC1 rs11615, rs3212986, and XRCC1 rs1799782, rs25487), but only ERCC1 rs3212986 was found to be significantly associated with the risk for malignant mesothelioma. However, this polymorphism was found to have a protective effect as carriers of ERCC1 rs3212986 heterozygous GT or homozygous TT genotypes had a decreased risk of malignant mesothelioma [115].…”

Section: Genes Involved In Dna Repair Mechanismsmentioning

confidence: 97%

“…Carriers of polymorphic ERCC1 rs11615 allele who were exposed to the low level of asbestos had a decreased risk of malignant mesothelioma. Based on these findings, it has been suggested that the genetic variability of DNA repair mechanisms could contribute to the risk of developing of this aggressive cancer [115].…”

Section: Gene-environment Interactions In Asbestos-related Pleural DImentioning

confidence: 99%

“…The results of the studies performed so far indicate that in addition to asbestos exposure, the genetic factors, as well as the interactions between genetic factors and asbestos exposure, may have an important impact on the risk of asbestos-related pleural diseases, in particular on malignant mesothelioma [102,115,120,121].…”

Section: Gene-environment Interactions In Asbestos-related Pleural DImentioning

confidence: 99%

“…Regarding asbestos-related pleural diseases, the interactions between genetic factors and asbestos exposure have been studied in the case of malignant mesothelioma [102,115,120,121].…”

Section: Gene-environment Interactions In Asbestos-related Pleural DImentioning

confidence: 99%

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Asbestos-Related Pleural Diseases: The Role of Gene-Environment Interactions

Dolžan¹,

Franko²

2020

Diseases of Pleura

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Several pleural diseases have been associated with asbestos exposure. Asbestos exposure may lead to the development of benign pleural diseases, such as pleural plaques, diffuse pleural thickening, and pleural effusion, as well as to the development of malignant mesothelioma, a highly aggressive tumour of the pleura. Asbestos exposure related to pleural diseases may be occupational or environmental. Although the causal relationship between asbestos-related pleural diseases and asbestos exposure has been well confirmed, the role of genetic factors in the development of these diseases needs to be further investigated and elucidated. The results of the studies performed so far indicate that in addition to asbestos exposure, genetic factors as well as the interactions between genetic factors and asbestos exposure may have an important impact on the risk of asbestos-related pleural diseases, especially malignant mesothelioma. This chapter aims to present how the risk of developing asbestos-related pleural diseases may be influenced by asbestos exposure, genetic factors, interactions between different genetic factors, as well as interactions between different genetic factors and asbestos exposure.

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Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP

et al. 2022

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Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a ban of using asbestos in many countries, the incidence of malignant pleural mesothelioma failed to decline worldwide. While little progress has been made in malignant pleural mesothelioma diagnosis, bevacizumab at first, then followed by double immunotherapy (nivolumab plus ipilumumab), were all shown to improve survival in large phase III randomized trials. The morphological analysis of the histological subtyping remains the primary indicator for therapeutic decision making at an advanced disease stage, while a platinum-based chemotherapy regimen combined with pemetrexed, either with or without bevacizumab, is still the main treatment option. Consequently, malignant pleural mesothelioma still represents a significant health concern owing to poor median survival (12–18 months). Given this context, both diagnosis and therapy improvements require better knowledge of the molecular mechanisms underlying malignant pleural mesothelioma’s carcinogenesis and progression. Hence, the Hippo pathway in malignant pleural mesothelioma initiation and progression has recently received increasing attention, as the aberrant expression of its core components may be closely related to patient prognosis. The purpose of this review was to provide a critical analysis of our current knowledge on these topics, the main focus being on the available evidence concerning the role of each Hippo pathway’s member as a promising biomarker, enabling detection of the disease at earlier stages and thus improving prognosis.

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The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma

Cited by 7 publications

References 32 publications

The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma

The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma

Asbestos-Related Pleural Diseases: The Role of Gene-Environment Interactions

Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP

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