While asbestos exposure causes the vast majority of mesothelioma cases, research has revealed genetic factors that influence who develops the disease. Understanding these factors may improve prevention, screening, and treatment.
Asbestos exposure remains the dominant cause of mesothelioma. Genetic factors primarily modify risk in exposed individuals or explain the minority of cases without known exposure.
BAP1: The Major Mesothelioma Gene
What Is BAP1?
Aspect
Detail
Full name
BRCA1-associated protein 1
Function
Tumor suppressor gene
Location
Chromosome 3
Discovery in mesothelioma
2011
Frequency in tumors
~60% have BAP1 alterations
BAP1 helps cells repair DNA damage and regulate cell growth. When BAP1 doesn’t work properly, cells are more vulnerable to becoming cancerous.
Somatic vs. Germline Mutations
Type
Meaning
Implication
Somatic
Acquired in tumor cells
Not inherited; affects only cancer
Germline
Present from birth
Inherited; cancer predisposition syndrome
Most BAP1 mutations in mesothelioma are somatic (not inherited). However, some patients carry inherited germline mutations.
BAP1 Tumor Predisposition Syndrome
Feature
Detail
Inheritance
Autosomal dominant
Mesothelioma risk
Significantly elevated
Other cancers
Uveal melanoma, kidney cancer, others
Screening recommended
For mutation carriers
Family testing
Important when identified
People with inherited BAP1 mutations have a lifetime risk of mesothelioma estimated at 6–7%, compared to less than 0.1% in the general population.
BAP1 and Treatment Response
Finding
Implication
BAP1-mutant tumors may respond differently
Treatment selection
Research ongoing
Targeted therapies in development
Immunotherapy response
May be affected by BAP1 status
Prognosis
Some studies show better outcomes
Lynch Syndrome and Mesothelioma
A New Connection
Recent case reports have documented mesothelioma in patients with Lynch syndrome:
Aspect
Detail
Lynch syndrome
Hereditary cancer predisposition
Primary cancers
Colon, endometrial, ovarian
Mesothelioma
Now recognized as possible
Mechanism
Mismatch repair deficiency
Frequency
Rare but documented
What Is Lynch Syndrome?
Feature
Detail
Cause
Mutations in DNA mismatch repair genes
Genes involved
MLH1, MSH2, MSH6, PMS2
Cancer risk
Multiple cancer types
Inheritance
Autosomal dominant
Prevalence
1 in 300 people
Lynch syndrome causes cells to accumulate DNA errors that should be repaired, increasing cancer risk throughout the body.
If you have mesothelioma without known asbestos exposure, multiple family members with mesothelioma, young-onset disease, or personal history of uveal melanoma, consider genetic evaluation. A genetic counselor can help determine if testing is appropriate.
Does genetics cause mesothelioma?▼
Asbestos exposure remains the primary cause of mesothelioma (80%+ of cases). Genetic factors primarily modify risk in exposed individuals or explain the minority of cases without known exposure. The BAP1 gene and Lynch syndrome are the most important genetic factors identified.
What is BAP1 and why does it matter?▼
BAP1 is a tumor suppressor gene that helps cells repair DNA damage. Mutations are found in ~60% of mesotheliomas. People with inherited (germline) BAP1 mutations have a 6–7% lifetime risk of mesothelioma versus less than 0.1% in the general population. BAP1 status may also affect treatment response.
Should mesothelioma patients get genetic testing?▼
Consider testing if you have multiple family members with mesothelioma, young-onset disease, no known asbestos exposure, personal history of uveal melanoma, or family history of BAP1-related cancers. Testing results can inform family screening and treatment selection.
How does Lynch syndrome relate to mesothelioma?▼
Lynch syndrome is a hereditary cancer predisposition affecting 1 in 300 people. Recent case reports document mesothelioma in Lynch syndrome patients. This is rare but important because MSI-high tumors (characteristic of Lynch syndrome) respond well to immunotherapy.