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DNA Mutation Research Reveals Why Most Smokers Never Get Lung Cancer
Scitechdaily ^ | 4.12.2022 | Albert Einstein college of medicine

Posted on 04/13/2022 6:41:44 AM PDT by libh8er

Cigarette smoking is overwhelmingly the main cause of lung cancer, yet only a minority of smokers develop the disease. A study led by scientists at Albert Einstein College of Medicine and published online on April 11, 2022, in Nature Genetics suggests that some smokers may have robust mechanisms that protect them from lung cancer by limiting mutations. The findings could help identify those smokers who face an increased risk for the disease and therefore warrant especially close monitoring.

“This may prove to be an important step toward the prevention and early detection of lung cancer risk and away from the current herculean efforts needed to battle late-stage disease, where the majority of health expenditures and misery occur,” said Simon Spivack, M.D., M.P.H., a co-senior author of the study, professor of medicine, of epidemiology & population health, and of genetics at Einstein, and a pulmonologist at Montefiore Health System.

Overcoming Obstacles to Study Cell Mutations

It’s long been assumed that smoking leads to lung cancer by triggering DNA mutations in normal lung cells. “But that could never be proven until our study, since there was no way to accurately quantify mutations in normal cells,” said Jan Vijg, Ph.D., a study co-senior author and professor and chair of genetics, professor of ophthalmology and visual sciences, and the Lola and Saul Kramer Chair in Molecular Genetics at Einstein (also at the Center for Single-Cell Omics, Jiaotong University School of Medicine in Shanghai, China). Dr. Vijg overcame that obstacle a few years ago by developing an improved method for sequencing the entire genomes of individual cells.

Single-cell whole-genome sequencing methods can introduce sequencing errors that are hard to distinguish from true mutations—a serious flaw when analyzing cells containing rare and random mutations. Dr. Vijg solved this problem by developing a new sequencing technique called single-cell multiple displacement amplification (SCMDA). As reported in Nature Methods in 2017, this method accounts for and reduces sequencing errors.

The Einstein researchers used SCMDA to compare the mutational landscape of normal lung epithelial cells (i.e., cells lining the lung) from two types of people: 14 never-smokers, ages 11 to 86; and 19 smokers, ages 44 to 81, who had smoked a maximum of 116 pack years. (One pack year of smoking equals 1 pack of cigarettes smoked per day for one year.) The cells were collected from patients who were undergoing bronchoscopy for diagnostic tests unrelated to cancer. “These lung cells survive for years, even decades, and thus can accumulate mutations with both age and smoking,” said Dr. Spivack. “Of all the lung’s cell types, these are among the most likely to become cancerous.”

Mutations Caused by Smoking

The researchers found that mutations (single-nucleotide variants and small insertions and deletions) accumulated in the lung cells of non-smokers as they age—and that significantly more mutations were found in the lung cells of the smokers. “This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized,” said Dr. Spivack. “This is likely one reason why so few non-smokers get lung cancer, while 10% to 20% of lifelong smokers do.”

Another finding from the study: The number of cell mutations detected in lung cells increased in a straight line with the number of pack years of smoking—and, presumably, the risk for lung cancer increased as well. But interestingly, the rise in cell mutations halted after 23 pack years of exposure.

The heaviest smokers did not have the highest mutation burden,” said Dr. Spivack. “Our data suggest that these individuals may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation. This leveling off of mutations could stem from these people having very proficient systems for repairing DNA damage or detoxifying cigarette smoke.”

The finding has led to a new research direction. “We now wish to develop new assays that can measure someone’s capacity for DNA repair or detoxification, which could offer a new way to assess one’s risk for lung cancer,” said Dr. Vijg.


TOPICS: Health/Medicine
KEYWORDS: apologists; dna; helixmakemineadouble; lungcancer; smoking
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To: libh8er
"Cigarette smoking is overwhelmingly the main cause of lung cancer, yet only a minority of smokers develop the disease."

This makes perfect sense. It says that of all the known causes of lung cancer, cigarette smoking is the leading cause. However, most cigarette smokers do not develop lung cancer.

In hypothetical terms, there may be 10 different known causes but nine of those ten may be at 5% each or 45%, which leaves the tenth at 55%. The "55%" of smokers who develop lung cancer represents the smaller percentage (a minority) of the total number of cigarette smokers because the study is based on a subset of cigarette smokers. The total number of cigarette smokers is not a factor but the subset is.
21 posted on 04/13/2022 9:42:09 AM PDT by equaviator (There's nothing like the universe to bring you down to earth.)
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To: cuban leaf

“Being afraid of smoking is like being afraid to ride in a car without a seat belt. Sure, you “might” die. But statistically you almost certainly will not.”

So why not reduce your odds of dying even further by not smoking and wearing a seat belt?

It’s not like smoking and not wearing seat belts are necessities.


22 posted on 04/13/2022 9:59:56 AM PDT by aquila48 (Do not let them make you "care" ! Guilting you is how they control you. )
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To: lee martell

I only smoke a little now, maybe 3 or 4 ‘sticks’ a day.

I Pity the poor soul who doesn’t have a bad habit to give up if they have a health problem.

paraphrase of Mark Twain.

I have been thinking lately I need a new bad habit, like finding my pipe and tobacco.


23 posted on 04/13/2022 10:06:39 AM PDT by PeterPrinciple (Thinking Caps are no longer being issued but there must be a warehouse full of them somewhere.)
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To: aquila48

So why not reduce your odds of dying even further by not smoking and wearing a seat belt?

It’s not like smoking and not wearing seat belts are necessities.


Though I agree in principle, the same can be said of alcohol, meat, salami, motorcycling, skiing, et al.

As Warren Zevon sez, “Life will kill you.”


24 posted on 04/13/2022 10:21:24 AM PDT by cuban leaf (My prediction: Harris is Spiro Agnew. We'll soon see who becomes Gerald Ford, and our next prez.)
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To: upchuck

You started smoking when you were 5?
And you are 87 now?
Or did you give us some phony numbers to see who is paying attention?


25 posted on 04/13/2022 10:46:57 AM PDT by Honest Nigerian
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To: cuban leaf

“As Warren Zevon sez, “Life will kill you.””

But some activities will kill you sooner than others.

But to each his own, as long as I don’t have to pay for it... which they’re making it harder and harder to do.


26 posted on 04/13/2022 10:51:50 AM PDT by aquila48 (Do not let them make you "care" ! Guilting you is how they control you. )
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To: aquila48

That’s why I’m not an ice climber. :)


27 posted on 04/13/2022 11:11:30 AM PDT by cuban leaf (My prediction: Harris is Spiro Agnew. We'll soon see who becomes Gerald Ford, and our next prez.)
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To: cuban leaf

Yep, the anti-smoking campaigns should have focused on how it affects your looks, not your health. IMO they would have been more effective.


28 posted on 04/13/2022 11:12:02 AM PDT by Yardstick
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To: milagro

It makes perfect sense. What it says is lung cancer is rare but the leading cause of it is smoking.


29 posted on 04/13/2022 12:46:13 PM PDT by muir_redwoods (Freedom isn't free, liberty isn't liberal and you'll never find anything Right on the Left)
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To: milagro
You're a good, word twisting democrat, Who slept through English grammar.


if

conjunction

In case that; granting, allowing, or supposing that; --

introducing a condition or supposition.Whether; --

in dependent questions.

30 posted on 04/13/2022 12:49:51 PM PDT by knarf (?<p>Little kids grow up to be adults that get into powerful positions and act out their thoughts.<pg)
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To: Honest Nigerian

Started around 1957. Quit in 1999. A smoker for around 42 years. I misfigured in the original comment. Thanks for noticing.


31 posted on 04/13/2022 5:14:27 PM PDT by upchuck (The longer I remain unjabbed with the clot-shot, the more evidence I see supporting my decision.)
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