The Puzzle of Lung Cancer in Nonsmokers.
by Rich Barlow
Originally published by BU Today on 1/22/13 at bu.edu.
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.”
Rebecca Kusko (MED’14) (left) spearheads research into lung cancer among nonsmokers in Avrum Spira’s lab. Photo by Vernon Doucette
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-inositol could 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 Beautiful had lung cancer.
The character was a nonsmoker.
Lung cancer programs receive a fraction of the grants devoted to types that take fewer lives, data show. The stigma of smoking looms large.
by Bridget Huber
This article was originally published in The Orange Country Register on November 15th, 2012.
Lung cancer takes more lives than any other cancer. This year it will kill an estimated 160,340 Americans – more than breast, colon and prostate cancers combined.
While lung cancer remains largely a death sentence – just 15.9 percent of those diagnosed are alive five years later – the federal government funds far less research on the disease than on other common cancers. The discrepancy is starkest when death rates are taken into account. In 2011, the two federal agencies providing most of the research money funded breast cancer research at a rate of $21,641 per death while spending $1,489 per lung cancer death.
It has been 41 years since President Richard Nixon signed the National Cancer Act, effectively declaring war on cancer. But there will be no victory without winning the battle against lung cancer, which causes more than one in four U.S. cancer deaths. Advocates say efforts to improve lung cancer patients' chances have been stalled by unexamined biases among health officials and the public as well as by scant research funds. They also cite the paradoxical invisibility of a disease that claims so many lives but has few champions of the sort who have brought breast cancer to national prominence.
The stigma of smoking is largely to blame. Anti-tobacco campaigns have done their job too well, leading many to see lung cancer as self-inflicted. That stigma keeps some families and patients from speaking out, while corporate donors stay away from the disease, and some scientists and policymakers question whether scarce research dollars should be devoted to a smokers' illness.
But an estimated 15 percent of lung cancers are diagnosed in people who never smoked. If lung cancer in these people was considered a separate disease, it would still be the sixth-leading cancer killer in the U.S., ahead of liver, ovarian and esophageal cancers. Researchers estimate that an additional roughly 50 percent of lung cancer cases involve former smokers who quit the habit years ago.
"This is a public health problem that needs to be addressed regardless of how it came about," said Dr. David Carbone, a leading lung cancer researcher at Ohio State University. "We need to take care of those who are sick and need to do everything we can from a public policy perspective to reduce the number of people at risk in the future."
Recent breakthroughs in cancer genetics and lung cancer screening have added urgency to advocates' calls for more money for lung cancer research, which will get $231.2 million this year from the two main federal agencies funding such work. "We are at a precipice where we could really break through," said Kim Norris, president of the Lung Cancer Foundation of America.
But these advances have come at a time when funding for all research is scarce. And many influential scientists balk at letting pressure from advocates influence research priorities. In their view, it could set the entire cancer research field back by creating a quota system for research on specific cancers that could divert funds from the most cutting-edge science.
Carbone, however, says unless a portion of federal funds is specifically directed to lung cancer, advances in the field will remain baby steps. "We didn't send people to the moon because we happened to have a rocket ship sitting around. We sent people to the moon by saying, 'That's what we want to do.' And then we figured out how to do it."
Making that moonshot will mean convincing the public and policymakers that lung cancer victims are worthy of support. Part of the challenge is that the disease is so deadly that there is no critical mass of survivors to raise its profile. Most people are diagnosed at an advanced stage and die within six months, said Jeffrey Borgia, a cancer researcher at Rush University Medical Center in Chicago. "There's not much time to fit a walkathon in," he said.
In contrast, breast cancer advocates have raised millions through everything from road races to galas. The White House is lit pink each October for Breast Cancer Awareness Month. Pink ribbons have been attached to items including pistols and fried chicken buckets, becoming so ubiquitous that some question whether the cause has become too commercialized. Lung cancer groups, however, have struggled to attract attention. The original color for lung cancer ribbons was clear – as in, invisible.
Perhaps the best example of how strong advocates can spur scientific research is the Defense Department's medical research program. In 1992, the National Breast Cancer Coalition, led by a breast cancer survivor and lawyer Fran Visco, persuaded the Defense Department to create a breast cancer research program funded by Congress. The resulting Congressionally Directed Medical Research Program has been allocated $2.8 billion for breast cancer research in the past two decades.
But even though the armed forces skew heavily male and military members smoke at high rates (cigarettes once were included in soldiers' rations and have been sold at cut-rate prices on military bases), it was 17 years before the program began researching lung cancer in 2009.
"It's really challenging now. There just isn't a champion," said Regina Vidaver, executive director of the National Lung Cancer Partnership.
The stigma problem
Before it can find its champion, lung cancer will have to shed its stigma. Last summer, advocates released an ad campaign aimed at shocking the public into examining its biases against people with lung cancer.
Posters featuring a young man with geeky glasses and a plaid scarf began popping up across the country. "Hipsters deserve to die," they read. "Cat lovers deserve to die," read another.
The point was provocation, said Kay Cofrancesco, a spokeswoman for the Lung Cancer Alliance, which sponsored the ads. When a person hears that an acquaintance has lung cancer, she said, a question immediately springs to mind: Did he or she smoke?
The answer often is no. Yet the stigma persists, even though lung cancer among nonsmokers is rising, with women accounting for two-thirds of these diagnoses. One famous example is Dana Reeve, the singer-actress and widow of Christopher Reeve. A nonsmoker, Reeve was just beginning to emerge from the grief of losing her husband when she was diagnosed with stage 4 lung cancer at age 44.
Yet blaming smokers who fell prey to cigarette marketing seems inconsistent – after all, society condemns tobacco companies for deceiving customers and even maximizing the addictiveness of cigarettes. We should "vilify the tobacco industry instead of vilifying patients," said Dr. Carolyn Dresler, an official with the Arkansas Public Health Department.
Lung cancer can be caused by such factors as exposure to radon, asbestos and other toxins. About 10 percent of lung cancer deaths are linked to heredity, said Ann Schwartz, a researcher at Wayne State University in Detroit. Yet lung cancer's image as solely a smoker's disease can undercut support for research that looks at other causes, such as heredity.
Changing the money
Many lung cancer advocates and researchers have called for a reassessment of the way money is distributed at the country's largest funder of cancer research, the National Cancer Institute.
Research grants from the NCI are the most important financing a cancer researcher can get. But the NCI's funding, allocated by Congress, has remained nearly flat since 2003, though it did get an additional $1.26 billion as part of the stimulus package of 2009.
Congress does not dictate how much NCI can spend on each type of cancer. Instead, NCI funds the cutting-edge science most likely to move the entire field of cancer research forward.
Lung cancer receives less funding than other cancers under this approach, too. In fiscal year 2012, the NCI will devote $221 million in research grants to lung cancer and $712 million to breast cancer, according to National Institutes of Health estimates.
NCI officials caution against reading too much into these numbers. Most of the research it funds is basic research applicable to multiple types of cancer. The institute also funds tobacco control and financed the National Lung Screening Trial, a large, multiyear study that showed that screening smokers via low-dose CT scans reduces the number of lung cancer deaths.
But some researchers, like Carbone, say the problem with the NCI's prerogative of funding the most advanced cancer research, regardless of what organ it involves, is that research on some types of cancer is further along than others. Breast cancer, for example, has been better funded for longer and had earlier breakthroughs that attracted more top researchers and more funding, from the federal government and other sources. "The infrastructure in the one disease is better than the other. It's a self-perpetuating problem," Carbone said.
Cancer research is increasingly focused at the molecular level instead of at the organ level. Researchers now know that cancers at different sites in the body can be caused by some of the same genetic mutations. But a single mutation can behave differently in different organs, so it is still necessary to look at particular cancers such as lung cancer, Carbone said.
The other side of the argument is represented by Dr. Harold Varmus, the NCI's director. He declined to be interviewed, but in a speech at the National Press Club in September, he said he would "object dramatically" to efforts such as legislation that would force the NCI to set aside specific pots of money for certain cancers. This approach, advocated by some groups over the years, would "take the decision-making about grant making out of the hands of the NCI and [put] it in the hands of advocacy groups," he said.
by By Lynne Eldridge MD
This article was originally published at About.com on
November 29th, 2012.
As Lung Cancer Awareness Month draws to a close I'm glowing from hearing about all of the events - and how each year there are more and more advocates investing their precious time and energy to spread awareness and provide funding for lung cancer research. But amidst that glow is a sadness. It seems just when I get excited about a new organization or another medical institution promoting awareness, I read the second line. "The key to reducing lung cancer deaths is to launch more anti-smoking campaigns."
Yes, those campaigns are important. But if we want to reduce lung cancer deaths, anti-smoking campaigns just aren't going to do it. Or even come close.
I'm sure many of you are saying, what in the world is she talking about?
A statistic may help:
Maybe a few numbers will make it even clearer. In 2008, the last year from which we have numbers available, there were 158,592 deaths from lung cancer in the United States, including 70,051 deaths in women. (Note that in the same year, there were 40,589 breast cancer deaths in women.) Using the 80% statistic, 126,874 of these deaths could not have been prevented by anti-smoking campaigns.
So why are we focusing on anti-smoking campaigns? Why are we focusing our attention on only 20% of people who develop lung cancer? Don't get me wrong. This group of 20% who are current smokers deserve our love and attention just as much. But what about the other 80%?
Since one of my pet peeves is listening to people rant who don't have a solution in mind, I'll offer a few.
Perhaps we should be focusing more attention on other known causes of lung cancer. Radon is the second leading cause and is totally preventable. Checking for radon in your home doesn't even take willpower. Occupational exposures need more attention as well.
And we need to focus more energy on treatment research. Even if we focus our efforts on the 20% with smoking cessation programs, many of those people will still develop lung cancer due to their history of smoking in the past.
To do this we need funding. To get funding, lung cancer needs to recognized.
Thanks to everyone who worked so hard to make this year's Lung Cancer Awareness Month more visible. Blessings to all of you.
PLEASE take time 2 watch these 2 inspiring & informative segments from KCBS @greatlungrun @jillslegacy #lungcancerawarenessmonthRead Now
By Chris Beattie, firstname.lastname@example.org
Originally published Friday, Oct. 26, 2012 on CarrolltonLeader.com (TX).
Lung cancer is the nation's No. 1 cancer killer. And that's not just of smokers.
McKinney resident Chris Haga knows first-breath just how little the disease discriminates.
"I am such an odd case," said Chris, diagnosed with Stage IV non-small-cell lung cancer (NSCLC) in July 2010. "I'm active, work out, in good health - and I've never smoked a cigarette. It was pretty devastating; I felt like I'd done everything I could not to get this form of cancer."
November is National Lung Cancer Awareness Month, and Chris is ever eager to get the word out: smoke or not, the disease is possible. And abundantly so in America. More than 226,000 people will be diagnosed with lung cancer this year - another person diagnosed every two minutes - according to an Uniting Against Lung Cancer report, which pulled from National Institutes of Health (NIH) and National Cancer Institute figures.
There aren't many campaigns, pink ribbons or races for lung cancer, though it surpassed breast cancer as the top cancer killer of women in 1987. Twice as many women die from lung cancer each year than from breast cancer, and close to 430 people die from it every day in the U.S., according to the report.
Between 15 and 20 percent of those diagnosed have never smoked, the report says, which is part of the reason more than half are diagnosed in later stages and just 15 percent are diagnosed when treatment would be most effective.
"I remember thinking for maybe two seconds that it could be lung cancer," said DeLayne, Chris' wife, of his early symptoms. "I dismissed that thought completely because he's never smoked."
Far from it, actually. Chris was riding his bike 80 miles a week when he got a weird cough in April 2010. He blamed it on allergies, and after it got worse, a doctor said he had an upper respiratory infection. Then after chest x-rays, it was determined pneumonia.
By July, as conditions worsened, it was time for a CT scan, which revealed a tumor on his right lung. Chris had a collapsed lung, and his second biopsy confirmed NSCLC, the most common type of lung cancer.
But his diagnosis wasn't complete. Further scans and MRIs at MD Anderson Cancer Center in Houston revealed a small brain tumor. The cancer had spread to lymph nodes in Chris's chest and abdomen.
His oncologist suggested he had a mutation known as EFGR, but medicine for that didn't work. Gamma Knife radiation killed the brain tumor, but post-radiation, Chris was sent to the emergency room because his lung tumor had grown and trapped fluid in his lung.
Dr. John Heymach, a thoracic oncologist on-call that weekend at MD Anderson, canceled Chris' impending port surgery and his first chemotherapy session. He suggested Chris might instead have the EML4-ALK gene mutation, and urged him toward a promising clinical trial.
"The treatment plan completely changed within what seemed like 30 minutes," DeLayne said. "Radiation to the lung began a few days later to immediately shrink the tumor so (Chris) could beat the pneumonia."
As he awaited an ALK analysis, Chris endured 15 rounds of radiation, including one that burned his esophagus so badly he could hardly drink water. He lost 35 pounds in a few weeks.
In November 2010, on his 51st birthday, Chris was told he was ALK-positive. Before his clinical trial started the following March, he went through three rounds of chemotherapy, and one chemo medication forced him to a hospital bed for a week. Tumors had spread to his lower left lung.
But his oncologist knew then that Chris was the first ALK patient he'd ever seen at MD Anderson. He's since reviewed other patients' records to test for the mutation.
Chris started taking Crizotinib (now Xalkori) in clinical trials. The medication targets the "Achilles' heel" of ALK-type lung cancers, according an American Cancer Society article from October 2010. That article said only about 2 to 7 percent of NSCLC patients has ALK aberrations.
Eunice Kwak, an oncologist at Massachusetts General Hospital, said in the article that the drug "will not cure advanced cancers with ALK abnormalities," but patients in the drug's study were taking it for close to two years.
Six weeks after Chris began taking it, there was no active tumor growth. At his 12-week checkup, his status was "in treatment with No Evidence of Disease" - what his physician's assistant deemed "as good as it gets" for advanced lung cancer patients. Doctors won't say a lung cancer patient is cured because it so often returns, DeLayne said.
Because he's part of the clinical trial, Chris gets the typically $10,000-a-month medication for free.
"All of the (doctors) have just been the right people in the right place at the right time for me to get on this medicine and enjoy life," Chris said.
An engineer with Texas Instruments, Chris recently began customer-quality engineering for medical groups that make CT scans, MRIs, products with which he's well acquainted. "I now have a vested interest in making sure they work properly," he said.
The Hagas understand the medicine is targeted therapy and may not work forever. The cancer could realign to a new genetic location and require different treatment.
But they're able to live a "pretty normal life," Chris said, one that includes spreading the word about an oft-ignored cancer. Lung cancer received just $1,420 of NIH funding per cancer death last year, nearly $18,000 less than breast cancer and $4,000 less than the next closest, colorectal cancer, stated the Uniting Against Lung Cancer report.
Other medications are being tested in clinical trials that are showing promise similar to Crizotinib.
Chris continues the ride, on and off the bike. He uses an incentive spirometer for daily breathing exercises. The meter range for a normal person is 2,000; he's been reaching 3,750 regularly and sometimes 4,000.
Those around the Hagas know that lung cancer doesn't pick its victims based on smoking habits. And that the race of life can go on.
"I'm able to do things that a lot of other cancer patients aren't able to do," Chris said. "I realize I'm a walking, talking, breathing miracle."
For more of Chris' story, visit his blog at http://CancerOn2Wheels.blogspot.com.
by Taylor Bell, Guest Blogger
The White House is “Pink” this month, but what will they do for Lung Cancer Awareness in November? NOTHING I’M SURE. Do people even know that November is Lung Cancer awareness month? Unfortunately, I doubt it. Sad. Pathetic. Hurtful. Shameful. Stigmatized. Unrecognized. Underfunded. Unimportant to Most.
Why? Because everyone thinks that in order to get Lung Cancer you have to smoke, and because you smoke you somehow deserve lung cancer. NO ONE deserves cancer of any kind. Not all smokers get lung cancer and not all lung cancer patients are smokers. Actually 60% of the newly diagnosed are NEVER smokers or former smokers who quit decades ago.
ALL cancers deserve the same recognition and awareness that breast cancer gets. We as a society do a disservice to the general public by hyping up breast cancer as much as we do and ignoring all of the other cancers that effect EVERYONE, specifically lung cancer. I’ve said it before but I am going to say it again. Lung Cancer is the NUMBER ONE cancer killer of MEN AND WOMEN in this nation. It kills more people than breast, prostate, colon and pancreatic cancers combined. It is the least funded of all major cancers and the stagnant 15.5% survival rate has remained unchanged for 40 years. 160,000 people will pass away from lung cancer this year alone in the US.
For those of you who don’t know, there is one person who is doing everything humanly possible to raise awareness for this disease. Kelcey Harrison is running across the UNITED STATES. Who can say they have done that? I would be surprised if anyone can say they have accomplished that task. 30-40 miles a day for 18 weeks straight….. What more could a person do to bring awareness to this horrible horrible cancer?! There is NOTHING more she could do. She is giving EVERYTHING possible.
ABC News Photo
So, why hasn’t the national news media picked up this story? Who knows? Is it because of the stigma? Is it because it’s not the “pretty pink cancer”? Is it because Lung Cancer doesn’t matter to most people? I mean, the girl is RUNNING ACROSS THE UNITED STATES. Why isn’t the TODAY Show, Good Morning America, Ellen, Oprah, Brian Williams, Rock Center begging her to be on their telecast? STIGMA. PERIOD.
That’s right folks, we have stigmatized this disease for so long that we have made everyone think that ONLY smokers get lung cancer and that they deserve it and therefore, Lung Cancer isn’t important.
Lung Cancer happens to people from all walks of life, Moms, Dads, Grandparents, Aunts, Uncles, Children, Siblings, Sorority Sisters, Division I College Athletes, NEVER SMOKERS, NFL Wives, Famous Singers and Actors, the list goes on.
From the great words of Katie Couric “It’s time to put the blame game aside, and figure out what is really going on.”
Please join me in trying to bring much needed awareness to Lung Cancer and bringing publicity to the one person who can say they have given everything humanly possible to raise awareness for this dreaded disease. Please follow @greatlungrun on Twitter or visit her website and fundraising page at www.thegreatlungrun.com and www.Crowdrise.com/thegreatlungrun.
Lung cancer rates are increasing among women and people who have never smoked, a new study finds.
Researchers from the French College of General Hospital Respiratory Physicians studied 7,610 lung cancer patients and 7,610 new cases of lung cancer in France in 2010.
The study found non-smokers made up 11.9 percent of the lung cancer cases, up from 7.9 percent in 2000. And the percentage of female lung cancer patients jumped from 16 percent to 24.4 percent over the decade.
Among women with a history of smoking, lung cancer rates barely changed over those 10 years, hovering around 65 percent. Meanwhile, this figure decreased in men, while the rate of male lung cancer patients who had never smoked increased, the researchers said.
Moreover, the study found changes in the severity of the cancer at the time of diagnosis.
"Not only has there been an increase in the number of women and non-smokers contracting the disease, but there has also been an increase in the number of cases diagnosed in stage 4 of the illness," lead researcher Dr. Chrystèle Locher said in a statement.
This change — 58 percent with stage 4 in 2010 compared with 43 percent in 2000 — might reflect new classifications of different stages of the disease, the researchers said. They also found big changes in the type of cancer being diagnosed. The rate of people developing adenocarcinoma, a form of non-small cell lung cancer, jumped from 35.8 percent to 53.5 percent over the decade.
Locher said more research is needed to understand what causes lung cancer in non-smokers, but she pointed to exhaust fumes from diesel engines as one possible factor. (The World Health Organization, WHO, recently classified diesel fumes as carcinogenic.)
Past research, presented in 2010 at a conference held by the American Association for Cancer Research, showed that lung cancer is different in non-smokers than in smokers, with non-smoker lung cancer tumors showing more than twice as many DNA changes as tumors in smokers.
To combat rising cancer rates among women, Locher said public awareness campaigns might help. "Anti-smoking campaigns must also target women more specifically, as we can see little change in lung cancer rates caused by smoking in women," the researcher said.
The results of the study were presented Tuesday, Sept. 4 at the European Respiratory Society's Annual Congress in Vienna. The research has yet to be published in a peer-reviewed scientific journal.
This article originally published on Sept. 4th, 2012 at LiveScience.com.