Key takeaways: Asbestos is a naturally-occurring group of minerals that was widely used in industry, construction, and transportation sectors until the early 1990s. Prior to the restrictions on its use, doctors and scientists established a definitive link between asbestos exposure and mesothelioma onset later in life. Some hypotheses that asbestos exposure cause mesothelioma–or carcinogenesis–discuss a disruption of the immune-mediated inflammatory response, the death of healthy tissues, and genetic mutations.
What is Asbestos?
Asbestos is a group of naturally-occurring minerals that was widely utilized for decades in the industries of production, construction, transportation, and personal protective gear. It was deemed a “miracle” by tradesmen and construction groups, given its remarkable durability, fire retardant properties, ability to insulate, and ability to be mined versus “built.” Asbestos was used in homes, schools, trains, cars, steel mills, shipyards, and more until the early 1990s when the Environmental Protection Agency intervened. Although asbestos use was regulated significantly, it’s still in use today by way of packaging, inadvertent contamination, and some construction materials (albeit in very minute amounts). Doctors and researchers established a link between asbestos exposure and mesothelioma as early as the 1970s. Although there was certainly a correlation between the two, doctors and scientists couldn’t firmly establish causation, meaning that they couldn’t pinpoint the exact reason asbestos ingestion led to mesothelioma (as opposed to leading to a different disease or being biologically inert).
Is There One Pathway of Carcinogenesis?
Carcinogenesis is the term ascribed to the development of a cancer–how it begins, its tendencies during growth, what resources it shunts away from the body, how it spreads (or doesn’t spread). Little was known about the carcinogenesis of mesothelioma, as mesothelioma is relatively rare and has a poor prognosis. However, contemporary studies are examining the microenvironments surrounding deposits of asbestos in patients’ lungs. Here are some of the projected carcinogenic pathways of asbestos into mesothelioma:
- Ingested asbestos causes human mesothelial (HM) cell death. HM are responsible for maintaining the slippery, protective serous membranes that line cavities and the spaces between internal organs. Some of the HM that evade asbestos-caused cell death become carcinogenic, as spurred on by local inflammation.
- Tumor necrosis factor-alpha (TNF-α) is a cytokine, or product of immune cells, that is released during inflammation. Outside of the mesothelioma lens, TNF-α is an exceptional recruiter of blood, nutrients, and immune attention to sites of inflammation (like a cut or broken bone). When asbestos is ingested, though, TNF-α gets hijacked: it incites a persistent inflammatory response at the site of asbestos. Unrelenting inflammation, scientists hypothesize, is a pathway of carcinogenesis.
- Genetic alterations as a by-product of the aforementioned–as well as other chronic inflammatory responses–are another way that mesothelioma develops. These genetic alterations affect a.) the frequency with which healthy cells divide; b.) their enabling of normal anti-cancer protocols; and c.) their programmed cell death (called apoptosis).
Can Asbestos Exposure NOT Cause Mesothelioma?
Yes. There are many documented cases of asbestos exposure that haven’t led to mesothelioma or any other asbestos-related disease; this makes tracking carcinogenesis even more difficult, as it seems only a sect of the population reacts to asbestos. Scientists hypothesize that there’s a genetic predisposition factor that people inherit, causing them to be more susceptible to environmental disruptions, called GxE hypothesis, or the gene-environment interaction hypothesis. If some people are more likely to develop mesothelioma based on genetic factors that doctors can test for, then the diagnostic realm can be revolutionized. Patients can be screened for alleles (versions of a gene) that are associated with mesothelioma, especially if they suffered known asbestos exposures. Genetic screening could significantly decrease diagnostic turnaround and could even act as a preemptive measure prior to mesothelioma onset.
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