Every time tobacco is inhaled, it creates conditions in the body almost ideally suited to the formation of cancer. So how do we explain lung cancer in non-smokers, and are there significant risk factors for lung
cancer other than smoking? We get to the bottom of this with Geoffrey Oxnard, MD, a medical oncologist at Dana-Farber's Lowe Center for Thoracic Oncology.
Read the transcript:
MEGAN: Hi, I'm Megan Riesz, and this is Cancer Mythbusters, a podcast from Dana-Farber Cancer Institute about the many myths and misconceptions in the world of cancer. Every episode, we'll look at a myth and debunk it with the
help of our world-leading clinicians and researchers.
Every time tobacco is inhaled, it creates conditions in the body almost ideally suited to the formation of cancer. And not just lung cancer — smoking is a risk factor for many different types of cancers, including throat, liver, pancreatic, stomach, cervical,
colon, bladder, and more.
The American Lung Association says that men who smoke are 23 times more likely to develop lung cancer than nonsmokers. However, lung cancer in never-smokers is the seventh most common cancer worldwide.
So, how do we explain lung cancer in nonsmokers, and are there significant risk factors for lung cancer other than smoking? We'll get to the bottom of this today with the help of Dr. Geoff Oxnard, a medical oncologist at Dana-Farber's Lowe Center for
Thoracic Oncology. Dr. Oxnard treats all types of lung cancer.
MEGAN: Thanks for joining me, Dr. Oxnard.
DR. OXNARD: Thanks for having me.
MEGAN: We know that smoking is the #1 risk factor for lung cancer. We hear this a lot, but what is it specifically about smoking that causes cancer cells to thrive?
DR. OXNARD: In part, smoking is a local irritant. The lungs respond to this chronic irritation, and the cells change. And through that changing and growing and re-growing, effectively, they can learn to keep growing. It's that perpetuation
of growth that can eventually become cancer. Additionally, smoking can impact the DNA itself, can damage the DNA, and through accumulating mutations over time, those DNA mutations lead to cell growth and then cancer and cancer metastasis.
MEGAN: If smoking is the #1 risk factor for lung cancer, how do you explain lung cancer in nonsmokers?
DR. OXNARD: I guess we kind of think there are two broad families of lung cancers. There are lung cancers that happen related to smoking, and there are lung cancers that happen related to the rest of bad luck. In fact, I tell my patients
that it's bad luck that causes lung cancer, and what we're just not totally sure of is what causes the bad luck.
Smoking is one of the causes. In lung cancers that occur in smokers, we see certain kinds of changes — more immune activation in lung cancer than we see in nonsmokers. We see other kinds of changes with certain genetic mutations that can be targeted with
But they can overlap, and in a smoker, you can get a nonsmoker's lung cancer, and in a nonsmoker, you could have exposures to get a more smoker's-related or smoker's-biology lung cancer.
MEGAN: Are there other risk factors that can explain lung cancer in someone who has never smoked?
DR. OXNARD: Epidemiologists have tried to find the other causes. Yes, some have been found. Other occupational exposures — inhalation of sand crystals or beryllium or asbestos, exposure to high doses of radon — but I don't think this
explains all the lung cancer in nonsmokers out there. In fact, a lot of the folks I see are young nonsmokers. There's just no environmental exposure that can really explain why this happened.
MEGAN: Are there inherited risk factors for lung cancer?
DR. OXNARD: We're trying to figure that out. A lot of the historic studies have looked at lung cancer in general, and in lung cancer in general, the dominant risk factor is smoking. We found some genes that make you smoke more. But again,
that doesn't explain a young nonsmoker I see who has lung cancer, her sister had lung cancer, and her mom had lung cancer.
We're trying to now find new genes that might explain these rare but unique families. We have a trial ongoing to study inherited mutations in a gene called eGFR.
We know eGFR is an important driver of lung cancer, but really rarely, it can actually occur in a patient's genes and can cause dramatic familial risk syndrome.
One of our ongoing efforts is to revisit the question of inherited risk now, using what we've learned about lung cancer biology to focus in on these unique families, where it appears recurrent lung cancer is occurring in various relatives who actually
MEGAN: What research are you working on to try to understand other risk factors for lung cancer?
DR. OXNARD: A lot of what I do is to try to look at the outliers and the people that don't fit. These may be rare genetic subtypes of lung cancer, where we're trying to find targeted therapies. One outlier group we're studying right now
is young lung cancer. Young lung cancer is one percent of lung cancer, but they're a motivated group. They're online, they're looking for an explanation as to why. What's the story with them? Because they're different.
We have this remote-enrollment study where patients who are diagnosed with lung cancer under the age of 40 can consent online, can get free genetic testing of their tumor, submit a blood specimen, and then we're going to try to figure out in this community
of patients if there is some inherited risk that explains why lung cancer happened in them.
We've got almost 100 patients now. It's really a very interesting way to try to do lung cancer research remotely, where we actually can bring the research to the patients, wherever they are around the world, and hopefully, by studying these people that
don't fit, we can start to change the narrative about why lung cancer happens and how to make it happen less often.
MEGAN: Some say that the stigma associated with smoking impedes research and can compromise patient care. Can you touch on this a little bit and give us some advice to lung cancer patients who are facing the stigma?
DR. OXNARD: You know, I think patients, when they get this diagnosis, it is, of course, a really big deal. It dramatically changes their understanding of their life and their health, but then the stigma makes them not talk about it, maybe
not look for treatment options, and maybe makes them less able to tap into the optimism that we have about treating this disease.
There are amazing advances. There are pill therapies. There are immune therapies. There are so many clinical trials. In fact, we've made more headway with lung cancer than perhaps any other cancer in the past years. That's really exciting for me. I think
there's so much happening that I want patients to be able to tap into that optimism, and I worry that the headwind of that stigma is that feeling of "This is something maybe I can't talk about, and maybe I won't get a good chance," because maybe there's
some guilt involved in this.
We need to stop that. The fact is that lung cancer, even when smoking goes away, was going to remain a really big health problem, and it's a health problem we're making headway on, hopefully, through the kind of research we're doing. We're looking at
people that don't fit, looking at familial lung cancer, looking at genetic subtypes. We're starting to change that narrative, and I think patients are really starting to benefit.
MEGAN: Thanks for joining us, Dr. Oxnard.
DR. OXNARD: My pleasure.
MEGAN: So, myth busted — smoking is not the only risk factor for lung cancer. There are lung cancers that are related to smoking, and there are lung cancers that (as far as researchers can tell right now) occur due to bad luck. A smoker
can get a nonsmoker's lung cancer, and a nonsmoker can be exposed to certain elements that lead him or her to develop a smoker's lung cancer.
That being said, there are many cases of lung cancer that are seemingly unexplainable. Researchers are exploring genes that might explain rare families of people that develop lung cancer, and they will continue to explore the question of inherited risk.
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