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Review
. 2021 Dec 17;18(24):13310.
doi: 10.3390/ijerph182413310.

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

Sonja Klebe  1   2 , Ashleigh J Hocking  2 , Matthew Soeberg  3 , James Leigh  3
Affiliations
Review

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

Sonja Klebe et al. Int J Environ Res Public Health. .

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.

Keywords: BAP1; RAD51; TP53; genetic predisposition syndrome; latency; mesothelioma; mesothelioma in situ.

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Conflict of interest statement

The authors S.K., M.S. and J.L. have provided reports on diagnosis and causation of asbestos-related disease to the courts and tribunals of Australia.

Figures

Figure 1
Figure 1
Chronic inflammation after asbestos inhalation causes DNA damage, leading to mutations and the proliferation of malignant cells. Apoptosis acts as a protective mechanism, removing damaged—and possibly malignant—cells. The genetic compromise in DNA repair and reduced effectiveness of the protective apoptotic mechanisms that normally safeguard the cell from malignant transformation would increase the speed at which mutations accumulated.
See this image and copyright information in PMC

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