Major cancer study shines light on UH

University of Hawaii researchers have helped discover a genetic mutation that makes people susceptible to a potent type of cancer, raising hopes that it will lead to gene therapies and drugs to prevent such cancers altogether.

The UH team also has patented techniques that might let people know if they’re genetically at risk for various cancers, especially mesothelioma, a disease most commonly associated with asbestos exposure that kills 3,000 Americans each year.

The discovery in December by researchers at the UH Cancer Center and the Fox Chase Cancer Center in Philadelphia follows 14 years of investigation by Dr. Michele Carbone — study leader and director of the UH Cancer Center — that began with the once-mysterious "Village of Death" in Turkey that has seen generations of deaths due to mesothelioma, an aggressive cancer that strikes the lining of the chest and abdomen.

Asked to compare the discovery of the BAP1 gene mutation with all of his other cancer research, Carbone called it "the most important one for sure," adding, "Now I have to decide what I’m going to do with my life."

Carbone need not worry.

He’s currently overseeing construction of the UH Cancer Center on the grounds of UH’s John A. Burns School of Medicine in Kakaako and is working to see whether the BAP1 genetic mutation discovered on the chromosome 3 tree is also linked to pancreatic, breast, ovarian and renal cancers.

"Now we have the possibility to identify people who are at higher risk for cancer," Carbone said Friday during an interview in his office in Kakaako over espresso and opera music. "This is going to be big."

The study of the BAP1 mutation will appear online Monday in Nature Genetics.

It’s based on genetic studies of separate families in Wisconsin and Louisiana that were exposed to natural and manmade asbestoslike materials and had suffered mesothelioma deaths through generations of their families.

Every family member with mesothelioma or melanoma of the eye also carried mutations in the BAP1 gene.

The research was funded by the National Cancer Institute, where Donald Blair, chief of the Cancer Etiology Branch, said in a statement, "The discovery that the BAP1 gene is involved in a new cancer syndrome characterized especially by uveal melanoma and mesothelioma provides yet another example of the critical importance of the detailed genetic analysis of human tumors. This is an important advance in developing our understanding of the biological mechanisms underlying these tumors."

Carbone’s interest in finding the cause of generations of mesothelioma deaths began on a 1997 visit to the Capaddocia region of Turkey, where 50 percent of the residents die of mesothelioma.

Homes in three tiny villages — Karain, Sanhidir and Tuzkoy, the "Village of Death" — were built out of erionite, a natural mineral that unleashes asbestoslike fibers when it’s broken up and formed into bricks or gravel.

But the ubiquitous presence of erionite in the Turkish villages did not explain why some homes were 100 percent devastated by mesothelioma for generations while others had no mesothelioma cases, Carbone said.

"Was there such a gene that could make some families more susceptible to cancer?" Carbone asked himself.

Erionite is found in rock formations and volcanic ash — and deposits also have been discovered in 12 American states, Carbone said. They include Oregon, Nevada and California.

Last year, Carbone’s team found levels of erionite in North Dakota that rivaled the levels he found in Turkey.

"It’s a very dangerous fiber, just as dangerous as asbestos," Carbone said.

Carbone later met with Turkish officials in his office in Kakaako and pressed them to relocate and rebuild the village out of modern materials — and build a cancer treatment center, which they did.

But legal and medical concerns prevented him from conducting genetic research on the Turkish families.

Then, four years ago, Carbone and his UH team were contacted by a family in Wisconsin that was hard-hit by mesothelioma and lived in a home insulated with an asbestoslike material called chrysotile. The team also was contacted by a family in Louisiana afflicted with mesothelioma that lived in separate homes covered by roofs made out of chrysotile and tremolite, another asbestoslike insulating material, Carbone said.

His team then pored over kilometers-long genetic sequences to try to identify a mutation in the families from Wisconsin and Louisiana.

For the first four years, Carbone’s team thought the genetic mutation was located on chromosome 6. When one of the family members developed mesothelioma — but did not have the same genetic mutation on chromosome 6 — the researchers then found that the mutation occurred on chromosome 3 in all of the mesothelioma cases they were studying.

"Everybody in the families that had cancer had the same genetic mutation," Carbone said. "If we could prevent those people from being exposed to erionite, then you would not see the devastating results of mesothelioma. Now we have the possibility to identify people who are at a higher risk of contracting cancer."

Currently, 27 million Americans are exposed to asbestos, Carbone said. And 25 million U.S. homes still contain asbestoslike materials, he said.

Genetic detection will alert people with the BAP1 mutation to avoid asbestos and similar materials and make life decisions such as avoiding construction jobs that expose them to similar building materials, Carbone said.

Patients with mesothelioma typically develop melanoma of the eye first, Carbone said.

When detected early, melanoma of the eye "is 100 percent treatable" and doesn’t even require surgery, Carbone said. Once it metastasizes to the liver, however, "you’re dead," Carbone said.

Carbone’s team is screening other members of the Louisiana and Wisconsin families "so they can hopefully modify their behavior and decrease their risk for cancer," Carbone said.

The Honolulu and Philadelphia teams that discovered the BAP1 gene mutation have since patented a screening test, Carbone said. And their discovery has the potential to lead to gene therapies and drugs to prevent the genetic mutation from developing into cancer, Carbone said.

Asked whether he’s about to become richer, Carbone laughed and said, "I hope that the University of Hawaii will make millions of dollars from this."