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Your Environment. Your Health.

Genetic Mutation Increases Mesothelioma Risk

Michele Carbone, M.D., Ph.D.
University of Hawaii at Manoa
R01ES030948

NIEHS grantees found that individuals with mutations of the BLM gene are more susceptible to developing mesothelioma, especially after exposure to asbestos, pointing to a gene-environment interaction. Individuals who inherit two mutated copies of the BLM gene have Bloom syndrome, a disease associated with increased cancer risk. This study showed that individuals with a heterozygous BLM mutation, meaning they only have one copy of the mutated gene, also have increased cancer risk.

The researchers sequenced the DNA of 155 mesothelioma patients, looking for heterozygous BLM mutations. Seven of the 155 patients carried such mutations, a significantly higher incidence than the expected frequency of 1 in 900 in the general population.

Using mice and human cells, the researchers determined that heterozygous BLM mutations lead to genomic instability following asbestos exposure. Additionally, in human cells with BLM mutations, asbestos exposure reduced cell death and altered inflammatory responses. The researchers exposed heterozygous BLM and wild-type mice to asbestos. Compared to the wild-type, BLM mutant mice had higher levels of inflammation markers, a hallmark of asbestos-induced cancer, and a higher incidence of mesothelioma.

Taken together, these results suggest that the probability of carrying heterozygous BLM mutations is significantly higher among mesothelioma patients than in the general population. In addition, BLM mutation carriers are at higher risk of developing mesothelioma — a risk that increases upon asbestos exposure. BLM mutation carriers may benefit from exposure prevention measures and screening for early detection, said the authors.

Citation: Bononi A, Goto K, Ak G, Yoshikawa Y, Emi M, Pastorino S, Carparelli L, Ferro A, Nasu M, Kim JH, Suarez JS, Xu R, Tanji M, Takinishi Y, Minaai M, Novelli F, Pagano I, Gaudino G, Pass HI, Groden J, Grzymski JJ, Metintas M, Akarsu M, Morrow B, Hassan R, Yang H, Carbone M. 2020. Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma. Proc Natl Acad Sci U S A 117(52):33466–33473.


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