Mesothelioma may be caused by exposure to ultramafic rock

Everyday exposure to naturally occurring asbestos increases the risk of developing malignant mesothelioma, according to a study by UC Davis researchers.

The study - the largest to examine the question - will be published this fall in the American Journal of Respiratory and Critical Care Medicine.

Exposure to asbestos in the workplace, particularly in shipyards, has long been recognized as a risk factor for mesothelioma, a rare form of cancer affecting the lining of the lung. But in the new study, researchers found a consistent and dose-dependent association between mesothelioma and residential proximity to ultramafic rock, the predominant source of naturally occurring asbestos.

"Our findings indicate that the risks from exposure to naturally occurring asbestos, while low, are real and should be taken seriously," said Marc Schenker, professor and chair of the UC Davis Department of Public Health Sciences and the study's senior author. "This study provides important supportive evidence that naturally occurring asbestos causes mesothelioma - and public efforts should now shift to understanding the risk and how we can protect people from this preventable malignancy."

To put the mesothelioma risk in perspective, the disease kills about the same number of Americans each year as passive smoking. About 2,500 people a year die from mesothelioma in the United States, according to National Institute of Occupational Safety and Health statistics. About 3,000 deaths a year are attributed to exposure to secondhand tobacco smoke, according to U.S. Environmental Protection Agency statistics.

Ultramafic rock is distributed throughout the Sierra Nevada, Coast Ranges and Klamath Mountains in Northern and Central California, and has been a source of increasing concern as new housing developments cut through these areas. Of most concern are the areas of ultramafic rock associated with tremolite asbestos.

In their ambitious study, Schenker and his colleagues used California Cancer Registry data to identify 2,908 cases of malignant mesothelioma diagnosed between 1988 and 1997 in adults ages 35 and older. In most cases, the registry also provided occupational history. As a control group, an equal number of age- and gender-matched pancreatic cancer cases was selected (since pancreatic cancer has no known association to asbestos exposure). For both the mesothelioma and pancreatic cancer cases, the researchers employed sophisticated geographic information system mapping to pinpoint home or street addresses for every diagnosed individual. A map from the California Department of Conservation, Division of Mines and Geology, served as the reference for ultramafic rock deposits. Finally, statistical adjustments were made for sex, occupational asbestos exposure and age at diagnosis.

The researchers found that the risk of developing malignant mesothelioma was directly related to residential proximity to a source of ultramafic rock. Specifically, the odds of having mesothelioma fell by 6.3 percent for every 10 kilometers (about 6.2 miles) farther a person lived from the nearest asbestos source. The association was strongest in men, but was also seen in women. No such association showed up in the pancreatic cancer group. The study was not designed to determine the "ground zero" risk for those living closest to an asbestos source - only to test for a relationship between proximity and risk.

"This is very creative, painstaking epidemiology," said Jerrold L. Abraham, professor and director of environmental and occupational pathology at SUNY Upstate Medical University in Syracuse, New York, and a leading authority on mesothelioma. "The UC Davis researchers have shown a significant association between living near deposits of naturally occurring asbestos and mesothelioma. This is the strongest evidence possible without conducting one-on-one interviews with each diagnosed mesothelioma patient or his or her family."

Laurel Beckett, professor and vice chair of the UC Davis Department of Public Health Sciences and a study co-author, said the findings are important. "We showed that breathing asbestos in your community is not magically different from breathing asbestos in an industrial setting. It would have been a surprise to find otherwise."

Similarly, she said, it was no real surprise to scientists when passive smoking was found to cause lung cancer. "Like smoking, exposure to asbestos appears to be very dose-dependent," Beckett said. "Day-in, day-out occupational exposures are more dangerous than intermittent exposures in the community. But the more you can do to reduce your personal exposure, the safer you will be."

While the overall mesothelioma rate was about one case per 100,000 people per year in the California study, the rate varied markedly by gender and age. For white males, the rate was 2.29 cases per 100,000. For white females, it was 0.49. People over age 60 had ten times the rate of those ages 40 to 59.

Worldwide, epidemiological studies of mesothelioma have found occupational causes for most but not all cases of the disease. In some undeveloped areas of the world, including parts of Greece and Turkey, mesothelioma cases have been linked to use of naturally occurring asbestos in household materials such as whitewash. The UC Davis study suggests naturally occurring asbestos also causes mesothelioma in developed countries, through incidental, non-occupational exposures.

California has required statewide cancer reporting since 1985 and established the California Cancer Registry in 1988. One of the largest cancer databases in the world, the registry is responsible for collecting cancer incidence and mortality statistics for more than one tenth of the United States population. An estimated 98.9 percent of all mesothelioma cases diagnosed in California are reported to the registry.

The registry's size enabled researchers to identify an association that might not have been apparent in a smaller study.

Needed now are field studies to more accurately characterize determinants of exposure to asbestos fibers among residents in areas with naturally occurring asbestos, Schenker said. In addition, he said more must be learned about the types and size of fibers in asbestos deposits, the types of human activities that disturb asbestos fibers and the determinants of cancer risk in exposed populations.

"Because mesothelioma takes 20 to 30 years to develop, what we learn today will allow us to protect Californians from this preventable cancer decades into the future," Schenker said.

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Nanotech could cause mesothelioma

Carbon nanotubes

3D model of three types of single-walled carbon nanotubes. (Wikipedia: Michael Stroeck, file photo)

In the 1990s scientists found a way to roll carbon atoms into a cylinder, called a nanotube. Now US researchers have found that the lungs of mice respond to some fibres from nanotubes as they would to asbestos, forming lesions and becoming inflamed.

Dr Andrew Maynard from the Woodrow Wilson International Centre for Scholars told AM nanotubes are excellent at conducting heat and electricity. They're already being used in sports equipment because of their strength.

"Almost like a miracle material. If only we could make it in large quantities in high purity, we could use it to do things that we have only dreamt of before," he said.

"If you look out in the market place, it is beginning to appear. So you can buy things like baseball bats, you can buy tennis racquets, you can buy golf clubs with this material, but I think those are probably just the tip of the iceberg."

Dr Maynard says at the moment there is no requirement to disclose that nanotubes are being used.

"In fact if you look at the safety guidelines for the material, most people are treating it just as graphite, the sort of stuff that you find in your pencil," he said.

He says the new study shows there is strong evidence that if carbon nanotubes get into the wrong place, they can cause mesothelioma.

"So we've got one piece of the puzzle here," he said.

"There are a couple of other pieces of the puzzle which still need to be filled in and those are asking whether exposure to this material actually will occur.

"Whether people can breathe it in and if they do, whether these fibres can work their way to the outer edge of the lung and then cause an effect.

"But we knew that if those two things happened, there is a very strong change that the prolonged carbon nanotubes will eventually lead to this disease."

Nanotubes used in sporting equipment are safely encased. Dr Maynard says the greater risk is to people involved in manufacturing them and disposing of them.

He hopes his findings aren't seen as fear-mongering, but he warns nanotechnology could become as widely used as asbestos once was.

"Carbon nanotubes are seen very much as the poster child of nanotechnology," he said.

"Some of the predictions are that by the year 2014 we are going to see goods sold around the world something like $2.6 trillion that are based in some way on different types of nanotechnology."

Dr Maynard also agrees there's a lack of knowledge about the safe use of nanotechnology in food, and is calling for more research.

"We are in a position where we could actually do great things with this technology if we had the knowledge to be able to use it safely," he said.

"Unfortunately, a lot of that knowledge is lacking at the moment. We need the research to fill in those information gaps."

Dr Maynard's findings are published today in Nature.

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Newest technique which can help diagnose mesothelioma

A new technique may help clinicians hone in on a diagnosis in patients presenting with a pleural effusion of unknown cause.

The study will appear in the Sept. 1 issue of the American Journal of Respiratory and Critical Care Medicine.

"Pleural effusion, or the accumulation of fluid in the pleural cavity, can be maddeningly difficult to diagnose as a wide variety of malignant and benign causes exist," said Helen Davies, specialist registrar and research fellow at the Oxford Center for Respiratory Medicine and Oxford University, lead author of the study. "One of the causes, malignant pleural mesothelioma, is a relatively rare cancer, but its incidence is rapidly increasing on a global scale."

Currently, the first-line test for mesothelioma in patients with a pleural effusion is pleural fluid cytology, but this test is not very sensitive. Dr. Davies and her colleagues undertook the study to determine whether there would be additional clinical benefit to looking at pleural fluid mesothelin, a protein released in high quantities into the pleural fluid of most patients with mesothelioma.

They obtained pleural fluid samples from 209 patients referred to a specialized respiratory clinic. Levels of soluble mesothelin were measured in all samples.

Their results demonstrated median pleural fluid mesothelin levels were over six times greater in patients with mesothelioma than in patients with metastatic carcinomas, and ten times greater than in patients with benign effusions.

Using mesothelin levels at a cut-off of 20nM, they found that it had an overall negative predictive value of 95 percent, meaning that a patient with a mesothelin level less than the cut-off of 20nM could be 95 percent confident they did not have malignant mesothelioma.

There were 12 false positive results with metastatic adenocarcinomas accounting for over 90 percent of these cases. However, all patients with pleural fluid cytology suspicious for mesothelioma and an elevated mesothelin level had mesothelioma.

"This study suggests a way for clinicians to more readily identify these cases from the start," said Dr. Davies.

Obtaining a prompt diagnosis of mesothelioma has benefits for patients and physicians alike. "Because mesothelioma has a median survival time of 12 months, minimizing the number of invasive procedures and tests patients require is crucial to reduce morbidity and the time they need to spend in hospital," said Dr. Davies. "An earlier diagnosis also allows speedier interventions to relieve symptoms as well as initiation of other treatments such as chemotherapy or radiotherapy if appropriate."

Exposure to asbestos is the main risk factor and accounts for the majority of mesothelioma cases. Legislation to prevent occupational exposure to asbestos has been enforced in the developed world; however, unrestricted contact continues in developing countries.

Over 90 percent of patients with mesothelioma present with a pleural effusion and its incidence is predicted to peak within the next two decades.

"Pleural fluid mesothelin provides a valuable adjunct in the diagnostic assessment of patients presenting with pleural effusions, especially when cytological examination is not definitive, and can improve clinical practice," said Dr. Davies.

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