Never Smoked. Lived Right. Died of Lung Cancer.

Avrum Spira’s aunt died of lung cancer almost 20 years ago. She was a nonsmoking exercise buff in her 40s who hadn’t been exposed to any known toxins; she worked in a government office, not a coal mine. “One of the healthiest people you could imagine, did everything right,” says Spira (ENG’02), who at the time was an internal medicine resident at the University of Toronto.

The one thing she didn’t do right wasn’t her fault: she’d been born to a nonsmoking mother who had died from the same illness. “I’m absolutely convinced she had a genetic predisposition” to lung cancer, says Spira, a School of Medicine professor and chief of computational biomedicine. That conviction set him on a quest for the genetic key to a medical mystery: why some people who have never smoked fall victim to this scourge of cigarette users.

Lung cancer kills more Americans than any other cancer, and twice as many women die from it than from breast cancer, although the latter gets greater public attention, says Spira. In 2008, the last year for which data was available, more than 208,000 Americans were diagnosed with lung cancer and almost 158,600 died from it. Spira says between 10 and 15 percent of these annual victims are nonsmokers (the percentage has been edging up slowly in recent years) with no apparent exposure to other toxins—a crucial caveat. “How do you know someone has been or has not been exposed to something in the environment?” he asks. Some potential toxins, like radon, are invisible, he notes, “so people who we’re seeing now, with higher rates of nonsmoking lung cancer—is it because they were exposed to radon 20 years ago?”

It’s true that worldwide, the rise in the incidence of lung cancer—from the eighth leading cause of death in 1990 to fifth in 2010—is mostly a function, perversely, of good news: as living standards have improved in the developing world, more people survive into adulthood, meaning a decline in childhood deaths from malnutrition and infectious diseases. That has brought an accompanying uptick in the number of people dying from diseases mostly found in wealthier countries, among them cancer. Moreover, air pollution in industrializing countries has resulted in more lung cancer in nonsmokers there, Spira says.

But in the United States, he says, doctors believe there’s a similar spurt in lung cancers in nonsmokers who’ve had no apparent contact with other toxins. The most extensive studies, incorporating detailed questionnaires and visits to peoples’ homes to see their environment, show that “there hasn’t been a clear association among nonsmokers who are getting lung cancer with exposures to other things.”

An ongoing, as-yet-unpublished study by a team that includes Spira is looking at tumor tissue and adjacent, noncancerous tissue from the lungs of 32 subjects with lung cancer: 8 smokers, 11 former smokers, and 13 who never smoked and had no apparent exposure to other toxins. The researchers ran the samples through a gene sequencer at MED, which “can give us unprecedented insight into the genomic changes leading to lung cancer” in nonsmokers, says Rebecca Kusko (MED’14), a graduate student spearheading the study in Spira’s lab.

With the sequencer, “we study the normal cells from each person as a control,” says Spira, “and then what happens in their tumor right next door, and say, what’s changed?” Preliminary results suggest that in the smokers, “a huge number of cancer pathways are activated,” as genes controlling cell growth in the tumors turned on. But those pathways weren’t necessarily activated in the nonsmokers, who showed different gene changes between their healthy lung tissue and their tumorous tissue. The researchers’ hypothesis is that the nonsmokers had a genetic predisposition, a pathway, to cancer that was activated by something in their environment.

That trigger, Spira theorizes, may be a viral infection (cervical, liver, and head and neck cancers are all caused by viruses, he says). The researchers are now sequencing the tumor tissue of the nonsmokers to try and find any viral genes. “Even if there’s one viral gene per million human genes, we might pick it up, we believe,” he says. The work will take a year or two.

Potential therapies—which are many more years away, he warns—might include screening people with the genetic predisposition and then giving those with the predisposition regular lung scans to catch cancers early. Another possibility would be drugs that could turn off uncontrolled growth in cancerous cells. (Spira got attention in 2010 for research suggesting that the natural compound myo-inositolcould turn off incipient lung cancer in smokers.)

Those who walk Commonwealth Avenue and have to dodge fumes from smokers on break may wonder about secondhand smoke. Research is mixed, but Spira, who researches the amount of smoke necessary to change gene expression and possibly lead to lung cancer, believes that it takes a big dose—perhaps exposure over months or years.

Almost half a century after the surgeon general first warned of smoking’s dangers, Spira says that even Hollywood is catching on that not all cancer victims heedlessly bring the disease on themselves. In 2011, he was a presenter at the Prism Awards, given for accurate portrayals of illness in entertainment media. He handed an award to an actress whose character on the soap opera The Bold and the Beautifulhad lung cancer.

The character was a nonsmoker.

Segregation tied to more lung cancer deaths: study

Black lung cancer patients seem more likely to die of the disease than white cancer patients in the U.S., especially those living in segregated counties, according to a new study.

Researchers, who published their findings in JAMA Surgery on Wednesday, found blacks patients living in segregated counties had a lung cancer mortality rate about 10 percentage points higher than those living in diverse neighborhoods during the mid-2000s.

That compared to white lung cancer patients whose lung cancer mortality rate did not seem to change between segregated and diverse areas.

"We first thought it was a mistake. We ran it five times through the program," said the study's lead author Dr. Awori Hayanga, a lung transplant fellow at the University of Pittsburgh Medical Center.

"If you are one color living in one type of neighborhood versus another, 10 percent is huge," he said.

According to the American Cancer Society, lung cancer is the leading cause of cancer deaths for both men and women. It kills more people than colon, breast and prostate cancer combined.

In 2013, the Society projects over 228,000 Americans will be diagnosed with lung cancer, and about 159,500 will die from it.

For the new study, Hayanga and his colleagues used national databases to collect information on lung cancer deaths in U.S. counties between 2003 and 2007. They also classified those counties as low, moderate and high segregated areas based on their concentration of one race versus another.

Nationally, black lung cancer patients had about a 59 percent mortality rate when the researchers accounted for smoking and income, compared to about a 52 percent mortality rate in white patients.

When looking at specific counties, the researchers found white lung cancer patients' mortality rate remained steady between diverse and predominantly white counties - between about 50 percent and 53 percent.

For black lung cancer patients, however, there were larger differences.

Black patients living in diverse counties had a mortality rate of about 52 percent, which was comparable to white patients.

But black patients living in highly segregated counties had a mortality rate of about 63 percent. Black patients living in moderately segregated areas had a mortality rate of 57 percent.

While the study cannot prove living in a segregated community caused the worse mortality rates in black patients, Hayanga said there is probably something different in predominantly black communities.

ENVIRONMENTAL VS. PATIENT FACTORS

"The point I'm trying to make is that neighborhood segregation is not just a proxy for socioeconomic status. We accounted for that," said Hayanga. "That's where we ask ourselves, do we know about the different fabric of different neighborhoods?"

He told Reuters Health that by comparing different counties, a person would find one has resources the other does not, such as hospitals and doctors.

The new study shows there are some health problems that can't be explained by genetics and treated with drugs, said David Chang, who wrote a commentary accompanying the work.

Disparities are "probably one of the issues that it's not the patients that matter but the systems," Chang, from the University of California, San Diego, told Reuters Health.

"Location matters, and one has to be critical about where they live and where they pay taxes," said Hayanga, who worked with Chang on previous research.

Dr. Karen Reckamp, a lung cancer specialist at City of Hope in Duarte, California, said there should be a focus on getting cancer care where it's needed.

"There is more technology in our healthcare and it's becoming more complex. People living in more remote areas wouldn't have the knowledge or access to seek out that care," said Reckamp, who was not involved with the new study.

She added that the new research doesn't answer what needs to change in those communities, but may shine a light on where the disparities are coming from.

"What we're seeing is that we can't uproot half of the American population and move them to other counties. What we have to do is take responsibility for those neighborhoods," said Hayanga.

NI hospital offers new procedure for diagnosing lung cancer

A new technique for detecting lung cancer without the need for surgery is helping patients in Enniskillen, County Fermanagh.

A thin flexible telescope, called an endobronchial ultrasound, is inserted through the patient's mouth and provides camera pictures and ultrasound images.

Samples can also be taken which can lead to faster diagnosis.

Dr Terence McManus uses the device in the South West Acute Hospital.

The 30-minute procedure is carried out under local anaesthetic and patients can normally return home the same day.

Dr McManus, a respiratory consultant, said: "It's a new technique that allows us to biopsy and diagnose conditions at an earlier stage.

"It can, in some cases, avoid the need for more invasive surgery techniques.

"Using this technique we can diagnose conditions such as cancer, inflammatory conditions, and sometimes infections as well."Lung disease

He said it allowed doctors to "establish a diagnosis and then determine what is the most appropriate treatment for a patient as quickly as possible".

Approximately 900 people in Northern Ireland are diagnosed with lung cancer each year.

It is the second most common cancer among men and the third most common among women.

Stephen Hogan from Florencecourt, County Fermanagh, has lung disease and has undergone the procedure.

He described it as very simple and added it had no unpleasant side effects.

"The big difference for me is knowing where I'm at with the diagnosis and the referral on to the oncologist and then I know what my treatment options are. So, it actually gives you a sense of relief and it saves a lot of time.

"I'm dependent on some degree of oxygen so travelling between A and B is a bit of an issue and we're very lucky to have this brand new facility, so it's brilliant."

The South West Acute Hospital, which opened its doors six months ago, is the first in Northern Ireland to offer this service.

Joe Lusby, deputy chief executive of the Western Health Trust, said it demonstrated how the latest technology is benefiting patients in the new state-of-the-art hospital.

"Anything that provides a faster and more accurate diagnosis of lung disease is bound to be good for the patient," he said.

"This hospital is built for the next 60 years at least so what we were doing is not just transferring services across from the former Erne Hospital.

"We were determined to add services that were appropriate to provide locally so that people don't have to travel great distances to access these services."

About 90% of lung cancer cases are caused by smoking cigarettes and Dr McManus has also seen patients getting the disease at a younger age.

He said: "It can affect any age. Smoking is certainly the biggest risk factor so we would always emphasise the importance of stopping smoking as soon as possible, it's never too late to stop smoking."

Soure