The Significance of Short Latency in Mesothelioma for Attribution of Causation: Report of a Case with Predisposing Germline Mutations and Review of the Literature

Our plain-English summary of The Significance of Short Latency in Mesothelioma for Attribution of Causation: Report of a Case with Predisposing Germline Mutations and Review of the Literature, by S. Klebe, A.J. Hocking, M. Soeberg, et al (International Journal of Environmental Research and Public Health, 2021).

The study

• Authors: S. Klebe, A.J. Hocking, M. Soeberg, J. Leigh
• Journal: International Journal of Environmental Research and Public Health
• Published: 2021;18(24)
• Type of article: Case report, Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is a tumour of the serosal membranes, related to asbestos exposure. Median latency is in the order of 40 years in various registries, but small numbers of cases with shorter latencies have long been reported and often dismissed as unrelated to asbestos exposure. However, emerging data regarding the significance of inherited mutations leading to a predisposition to mesothelioma suggest that the causative effect of asbestos may be associated with shorter latencies in a subset of patients. Here, we describe a male patient with germline mutations in RAD51 and p53 who developed peritoneal mesothelioma 8.5 years after well-documented asbestos exposure and discuss the current literature on the subject. Mesothelioma in situ is now a WHO-accepted diagnosis, but preliminary data reveal a potential lead time of 5 or more years to invasive disease, and this is also a factor which may affect the recording of latency (and potentially survival) in the future.

In plain English

This article combined a report of one patient with a review of published literature on short latency (the time from asbestos exposure to diagnosis) in mesothelioma. The patient grew up in Europe and had no asbestos exposure in his earlier jobs. At age 55 he worked for about 3 to 4 months as a truck driver for a demolition company, breaking up asbestos-cement sheets by hand without protective equipment. No fiber type was given. He was diagnosed at age 63 with epithelioid peritoneal mesothelioma, 8.5 years after that exposure. He had no family history of cancer. At age 57 he had a low-grade neuroendocrine tumour of the small bowel removed. Sequencing found inherited (germline) mutations in RAD51D and TP53, and acquired tumour mutations in NF2 and BAP1. The review summarised earlier reports of latencies under 10 years. The authors concluded that genetic predisposition provides biological reasons for short latency in some patients, and that germline testing may help assess a possible causative role. They acknowledged that an earlier, unrecorded exposure is always possible.

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: Case report of a single patient (including whole-genome sequencing of tumour tissue and blood) combined with a narrative review of the literature on short latency
• Who was studied: One male patient who grew up in Europe and was diagnosed with peritoneal mesothelioma at age 63; the article does not state the country of diagnosis
• Exposure: About 3 to 4 months of work at age 55 as a truck driver for a demolition company doing asbestos removal. He broke up asbestos-cement sheets by hand and loaded debris, without protective equipment. The fiber type is not stated, and he had no asbestos exposure in earlier jobs.
• Main results:
  • The patient was diagnosed with epithelioid peritoneal mesothelioma at age 63, 8.5 years after the documented asbestos exposure.
  • The patient had no family history of cancer, and a low-grade neuroendocrine tumour of the small bowel ('carcinoid') was completely removed at age 57.
  • Germline sequencing in the patient found a pathogenic mutation in RAD51D that results in a truncated protein, and a TP53 missense mutation.
  • The tumour showed loss of BAP1 protein on staining, matching an acquired (somatic) BAP1 mutation found by sequencing; an acquired NF2 mutation was also found.
  • In the review part, the authors summarised earlier published reports (case reports, registries, cohort and case-control studies) describing latencies of less than 10 years.
  • The authors noted reports that progression from mesothelioma in situ to diffuse mesothelioma can take 5 years or more. They said earlier diagnosis may mean future recorded latencies no longer match accepted latency periods.
• The authors' conclusion: The authors concluded that studies of genetic predisposition provide biological reasons for relatively short latencies in some patients, and that germline genetic assessment may help determine a possible causative role in such patients.
• Limitations the authors state:
  • The authors acknowledged that it is always possible an earlier asbestos exposure was not accounted for.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Latency, Mesothelioma, Attribution, Causation, Germline Mutation, Asbestos Exposure, Peritoneal Mesothelioma, Mesothelioma in Situ.

Related studies

• Well-differentiated papillary mesothelioma: clustering in a Portuguese family with a germline BAP1 mutation — C. Ribeiro, S. Campelos, et al. (2013)
• Detecting germline BAP1 mutations in patients with peritoneal mesothelioma: benefits to patient and family members — M. Kittaneh, C. Berkelhammer (2018)
• Germline BAP1 mutations predispose to malignant mesothelioma — J.R. Testa, M. Cheung, et al. (2011)
• Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma — V. Panou, M. Gadiraju, et al. (2018)
• Germline mutation of Bap1 accelerates development of asbestos-induced malignant mesothelioma — J. Xu, Y. Kadariya, et al. (2014)
• Bap1 Is a Bona Fide Tumor Suppressor: Genetic Evidence from Mouse Models Carrying Heterozygous Germline Bap1 Mutations — Y. Kadariya, M. Cheung, et al. (2016)

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