Mesothelioma Risk from Limited Asbestos Exposure

Doctors have long known that asbestos exposure in the workplace significantly increases the risk for mesothelioma, but now they’ve discovered that even workers who have had relatively low exposure to asbestos are at increased risk for this deadly cancer, according to a study in the Journal of Occupational and Environmental Medicine. The study also suggests that the man-made fibers often used to replace asbestos in manufacturing may also be increasing workers’ mesothelioma risk.

Most asbestos cases including mesothelioma have been linked to occupational asbestos exposure, and particularly from exposure to the amphibole type of asbestos. Still uncertain is the risk from man-made vitreous fibers (MMVF), which are often used as a substitute for asbestos. MMVFs are similar in structure to asbestos, and some researchers have theorized that they also can cause cancer, but there hasn’t been enough research done to confirm this potential risk.

“Research into the environmental or occupational causes of cancer is difficult to conduct, for various reasons, and there are too few qualified researchers in the entire area of environmental causes of disease,” explains study author Jack Siemiatycki, PhD, Professor at the University of Montreal in Canada. “While many people think that there are armies of researchers investigating such questions, in fact there are only a small number throughout the world, for all environmental chemicals combined. Thus, even though asbestos is the most-studied occupational carcinogen, there still remain unanswered questions about how and under what conditions the different forms of asbestos can cause cancer (such as mesothelioma), and whether MMVF is equally dangerous.”

In the 1980s and 1990s, Professor Siemiatycki and his colleagues launched two studies examining the link between occupational exposures and cancers such as mesothelioma. In these studies, mesothelioma patients were asked about their lifestyle and work histories. Their health and occupational histories were matched with those of healthy controls and other cancer patients. A team of experts then reviewed the responses and compiled a list of potential occupational exposures, including asbestos and MMVF.

Exposed participants were divided into two groups: Substantial exposure included participants who had been exposed to medium or high concentrations of asbestos for more than 5% of their work week for five years or more. Participants who were exposed to lower concentrations of asbestos for a shorter period of time were considered to have had nonsubstantial exposure.

In this study population, the workers most likely to be exposed to both asbestos and MMVF were plumbers and pipe fitters; whereas mechanics were the most likely to be exposed to asbestos alone.

The authors discovered a significantly increased risk of mesothelioma among participants who had occupational exposure to asbestos, and particularly among those who were exposed to the amphibole form of asbestos. However, even workers with nonsubstantial exposure were at higher risk for mesothelioma, which hadn’t been found in previous studies. This discovery suggests that more needs to be done to protect workers from on-the-job asbestos exposures. “As with any other potentially harmful exposure, workers’ exposures should be minimized to the extent that technology and finances permit,” Professor Siemiatycki says.

Another unexpected finding of the study was that participants who were exposed to both asbestos and MMVF were at higher risk for mesothelioma than those exposed to asbestos alone. This suggests that the two substances might work synergistically to increase mesothelioma risk, although the authors say more research is needed to confirm this theory.

“Because of the increasing use of and exposure to MMVF, and the lingering exposure to asbestos, it is important to pursue research to better understand how exposure to these various fibers, alone and in combination act to influence risk of mesothelioma,” the authors wrote.


Source:
Pintos J, Parent ME, Case BW, Rousseau MC, Siemiatycki J. Risk of mesothelioma and occupational exposure to asbestos and man-made vitreous fibers: evidence from two case-control studies in Montreal, Canada. JOEM. 2009.51:1177-1184.

© Surviving Mesothelioma and Cancer Monthly. All rights reserved.

Mesothelioma and Other Cancers Caused by Asbestos Through DNA Damage

Exposure to crocidolite asbestos triggers enhanced DNA damage that can turn cells cancerous, according to a study published online September 25 in the American Journal of Respiratory Cell and Molecular Biology. The discovery might one day lead to a new method of screening people who have been exposed to asbestos and are at risk for mesothelioma and other cancers.

The connection between asbestos and cancers such as mesothelioma has been well documented. Because decades can pass before asbestos-related cancers are diagnosed, and patients with mesothelioma survive an average of just a few years, it is crucial to identify signs of increased cancer risk as early as possible. One way might be to look for DNA damage in patients who have been exposed to asbestos.

Crocidolite asbestos is thought to be the most dangerous form of this fibrous mineral. It leads to the creation of harmful molecules called reactive oxygen species (ROS) and triggers DNA damage that can cause normal cells to turn cancerous. The body tries to repair that damage, but it isn’t always successful. This can lead to the creation of cancer like mesothelioma.

DNA is made up of a two-stranded double helix. When only one of those two strands is defective (called a single strand break), the other strand can be used as a template to repair the broken strand. When both strands are broken (called a double strand break), the body has more trouble fixing the damage. “As a result of not being repaired, the DNA can give rise to mutations,” says study author Val Vallyathan, PhD, Team Leader in Pathology and Physiology Research at the National Institute for Occupational Safety and Health, and Professor of Pathology at West Virginia University. Those mutations can lead to mesothelioma and other cancers.

Dr. Vallyathan and his colleagues looked at the ability of three substances—crocidolite asbestos, silica, and titanium dioxide—to trigger DNA damage in cells, and the genetic ability to repair that damage. Asbestos has already been proven to cause mesothelioma and lung cancer. Dr. Vallyathan included silica and titanium dioxide in the study because their cancer-causing potential is still widely debated.

“Silica is not fully confirmed as a carcinogen in humans, although several studies have shown that it is,” he says. “Titanium dioxide had been considered a very inert particle and had been used as a negative control in animal studies and cellular studies, but in recent years it has been shown that it is probably more toxic than what it was thought to be.”

The researchers exposed normal airway cells and lung cancer cells to all three substances. Although crocidolite asbestos, silica, and titanium dioxide all triggered DNA damage, asbestos was by far the most toxic to cells. It produced the highest amount of ROS production, and led to more DNA double strand breaks than either silica or titanium dioxide.

Asbestos caused continuous DNA damage in both the normal and cancerous cells, which the cells were unable to repair. That second hit of damage to already cancerous cells indicates that asbestos could trigger additional changes inside those cells, leading to more aggressive cancers like mesothelioma that are more likely to spread, Dr. Vallyathan says.

The authors say detection of DNA double strand breaks could be used to measure potential cancer risk in people who have been exposed to crocidolite asbestos. Dr. Vallyathan says that in future research, he would like to monitor the blood of people with known exposures to carcinogens such as asbestos, to determine whether DNA damage can be detected early.

Source:
Msiska Z, Pacurari M, Mishra A, Leonard SS, Castranova V, Vallyathan V. DNA double strand breaks by asbestos, silica and titanium dioxide: possible biomarker of carcinogenic potential? Am J Respir Cell Mol Biol. 2009 Sep 25.
© Surviving Mesothelioma and Cancer Monthly. All rights reserved.