Genetic Links to Mesothelioma in Younger Patients

Mesothelioma, a rare and aggressive cancer that is strongly linked to asbestos exposure, is increasingly being diagnosed in younger patients. This trend is perplexing given the well-established latency period of asbestos-related cancers, typically occurring 30-60 years after initial exposure.

A recent article published in PNAS by Flavia Novelli et al. sheds light on this mystery. By using SALSA^® digitalMLPA™ Probemix D001 Hereditary Cancer Panel 1, the researchers found that approximately 1.8% of all mesothelioma patients, and 4.9% of those younger than 55, carry rare germline variants of the BARD1 gene, which are predicted to be damaging. Through functional cell assays, they discovered that cells with these BARD1 variants exhibit genomic instability, reduced DNA repair, and impaired apoptosis. Further investigation revealed that BARD1, p53 and SERCA2 form a trimeric protein complex, which regulates crucial cellular processes.

This study indicates that the identified genetic variants increase susceptibility to asbestos carcinogenesis and favour the development of mesothelioma, albeit a less aggressive form compared to mesothelioma observed in older asbestos workers.