Can doctors tell when cancer is caused by something specific, such as smoking or chemicals?

Submitted by [deleted] t3_1167r4w in askscience

Me (a nicotine vaper) and my friend (a cigarette smoker) were talking about smoking/vaping and the pros, cons and reasons to quit or switch. Cancer came up, of course, and my friend wondered if doctors can tell when a cancer associated with smoking (like lung or mouth/throat) are caused by it, even if a person lies and says they never smoked a cigarette in their life.

Now I'm curious if that's not only possible for smoking-caused cancers, but other cancers associated with specific things, like chemicals found in war weapons and weed killers.

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0oSlytho0 t1_j969ls5 wrote

Short answer: no.

but some mutations are more likely in smokers, others in drinkers, drug users etc etc etc. A whole bunch of statistics can show these patterns.

Back from patterns to the individual; Definite proof that your tumor came from smoking is, again, not possible. But it's a likely factor that had an influence.

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shaokim t1_j99heib wrote

To add to this: we can't determine the exact reason why cancers were caused in the great majority of cases. However, there are cases and certain types of cancer where we can determine with great confidence that a certain cause was at its origin.

For example, in cervical cancer, usually caused by a virus called Human Papilloma Virus, that same virus leaves a kind of hallmark when viewed under the microscope called a koilocyte. AFAIK, detecting cancer of squamous cells in the cervix together with koilocytes OR the actual isolation of the virus is pathognomonic for HPV-caused cervical cancer.

For people with familial cancer syndromes, like Familial Adenomatous Polyposis (FAP), if a person comes in at an early age ie. 25 years old, and we see on colonoscopy a colon that is littered with growths, and after biopsy one of those growths comes back as malignant, we can tell with a high degree of certainty that the familial cancer syndrome (the heritable gene defect) was at the cause of the cancer.

Another type is a mucosa associated lymphoid lymophoma of the stomach. If we find a bacterium called Helicobacter pylori in the stomach, together with a tumor we determine to be a MALT lymphoma, and especially if that tumour regresses in antibiotic therapy, we can determine with high certainty that H. pylori caused that exact tumour, IIRC.

Actinic keratosis is a skin condition that's caused by chronic excess UV-exposure (usually the Sun). It can lead to the development of skin cancer. If skin cancer arises from actinic keratosis, we can say with a high degree of certainty that UV light caused it.

There are many more examples: liver cancer in a patient with an alcoholic cirrhotic liver; esophageal cancer on the part closest to the esophagus in know stomach acid reflux, etc etc…

these may not be ‘caused by this definite exact cause’ but ‘caused by this to a high degree of certainty’.

There's bound to be more examples in genetic cancer syndromes (such as Li-Fraumeni, Multiple Endocrine Neoplasia) and infectious cancer syndromes.

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MarineLife42 t1_j96fer2 wrote

No.
In medicine, you always have to distinguish between a cause and a risk factor. When you fall off your bike and break your arm, then the fall was the cause, as it led directly to the injury. SARS-CoV-2, the virus, is the cause for Covid 19, the illness.

Smoking, however, is a risk factor. Take lung cancer: non-smokers can absolutely contract it, but it is actually quite a rare disease for them.
For smokers, it is a very frequent disease but only some of them get it, not all of them. So, smoking greatly increases your risk of lung cancer. Nevertheless, if you have a particular patient in front of you who A., has lung cancer and B., is or was a smoker, you cannot prove that the smoking caused the cancer. It is awfully likely but there is always a (small) chance that the individual might have contracted cancer without smoking anyway.

That said, as far as risk factors go smoking is right up there with the big ones, secod only to (maybe) obesity. Smoking greatly increases your risk of:

  • cancers of the lung, mouth, tongue, throat/lanrynx, esophagus (food pipe), trachea (wind pipe), stomach, intestinal tract, kidneys, and bladder, and probably a few more,

  • heart disease (both heart attack and heart failure),

  • stroke,

  • COPD (Chronic Obstructive Pulmonary Disease), which few smokers have on their radar but is actually affecting millions and millions of smokers. It is what you get when a lung damaged by years of cigarette smoke goes into a downward spiral of infection and re-infection. There is no cure. Sufferers get shorter of breath little by little until, finally, their weakened hearts give out.

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DenseHovercraft2288 t1_j96yz4x wrote

Only like 10-15% of smokers get lung cancer, so it's not that common with them as well. Most end up dying of vascular diseases and lung diseases.

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darthaxolotl t1_j979ai4 wrote

Wow, wow, wow -- 10-15% of smokers get lung cancer that is A LOT. Yes, most of them end up dying of vascular or lung disease other than cancer (and probably some of those that died of heart attacks also related to their smoking would have gone on to get lung cancer). In non-smokers the number of primary lung cancers is <<1%.

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Unlikely_Plankton_11 t1_j989zk0 wrote

It's a lot for sure. Huge number. It's just kind of less than you would have thought. And keep in mind that the category of "smokers" has both those who smoke a pack a week and those who smoke 5 packs per day.

Even if you smoke a pack a day for 20 years, your risk of getting lung cancer - while way higher than someone who has never smoked, is still surprisingly low in an absolute sense. I would have thought it'd be like 80% or something. Not the case. It turns out that as far as smokers go, a pack a day is "light."

All of the other health effects, however, are honestly a much more compelling reason to quit. It's easy to brush off an elevated but still unlikely death by cancer. But it's not like you're fine and then you just up and die one day when you're 85. That honestly wouldn't be so bad at all. Much more common is that you'll live much of your life with weird chest pains, coughing every morning, getting out of breath going on walks, etc. Planning your life around smoke breaks and not smelling like smoke before going to the office or on a date, keeping your car/house from smelling like smoke, etc. Your QOL goes way down long before you get cancer - if you ever even do.

That was what motivated me to quit smoking when I was 26. And uh...again when I was 32 (though I quit for 2 years in the middle). I could feel that I was a smoker, and that was scary. You're not supposed to feel sick when you take a deep breath.

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Indemnity4 t1_j98ec6u wrote

Statistics are great fun!

About 20% of the lung cancer deaths in the USA are non-smokers, or ~7000 people a year.

While lots of people know about smoking=cancer, most don't know about smoking=COPD or heart disease. Cancer sure is up there as the scariest, but it's not the thing that will probably kill you.

Crudely, very roughly taking those numbers: smokers are ONLY 4X more likely to die from lung cancer than general population. That's, surprisingly not that much higher. There are way riskier activities such as SCUBA diving or living near a busy road.

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redligand t1_j97jyah wrote

It is a lot, yes. But they still have a bit of a point. In absolute terms lung cancer isn't hugely common in smokers. About 1 in 10. So you're still somewhat unlikely to get lung cancer as a smoker. Although you're massively more likely to get it compared with someone who has never smoked. So it's a huge relative risk but a somewhat low absolute risk. As an individual even if you smoke the odds are still in your favour wrt lung cancer. Of course, with smoking there is a bunch of other things that can kill you before you get the chance to win the prize of lung cancer. So that has to be considered too.

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thecooliestone t1_j97qxei wrote

No.

Even if they could, how could they tell if it was you smoking or second hand smoke?

I have lung issues from second hand smoke and every time I go to a new doctor they ask if I smoke and kind of don't believe me until I say both my parents did my entire childhood in the house and in cars.

Maybe your parents smoked. Maybe a spouse does. Maybe you just worked in a smoking bar. Who could tell?

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ParkieDude t1_j9hasxw wrote

Lung Cancer. Non smoker. Adenocarcinoma, so roughly five types, each with 20 sub-types. NSCLC > Adenocarcinoma > about 100 variations. Take about a crash course with oncology.

About 20% with lung cancer have no known cause.

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SuburbanSubversive t1_j96d96l wrote

Usually not. There are some cancers that are very linked to occupational or specific exposures (mesothelioma in people exposed to friable asbestos, for example).

The links between most cancers and environmental or behavioral exposures (like smoking or other chemical exposures) are determined statistically by epidemiologists, who observe higher incidence of the cancer in a group of people exposed to a certain thing. These higher rates of cancers have to be 'real' - that is, not just due to random chance. Epidemiologists use statistical methods to show this, and their data covers entire populations, not individual people.

Part of the reason a doctor can't usually tell someone what caused their individual cancer is that people vary. There are lifetime smokers who never get lung cancer and people who have never smoked who do. Cancer in general appears to be caused by a complex interaction between a person's genes, their exposures, time, etc.

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[deleted] OP t1_j96ql26 wrote

What I'm reading is we need to invest in brain uploading technology and leave our limited mortal coils behind

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Pugzilla69 t1_j981evc wrote

To some extent. Characterstic mutations in certain cancers can be associated with specific etiologies.

Angiosarcomas with MYC amplificaton are associated with radiotherapy and lypmhedema.

p16 positive carcinomas are almost universally caused by HPV.

Burkitt Lymphoma with EBER positivity is caused by EBV.

There are many more.

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tinkh t1_j975dob wrote

We all know when people lie about smoking. The “social smoker”. How we know?

Respiratory and Pulmonology providers. Decreased DLCO that is caused by destruction of the lung surfaces when it is combined with air trapping and obstructive disease showing on Pulmonary Functions Tests which anyone going through lung cancer will know. Through EBUS, Navigational Bronchoscopes, and traditional methods of biopsy, we obtain cells that will be staged and identified. Your carboxyhemoglobin being over 5.0 we know you smoked or were in a house fire. We may not our heads like we believe you, but we absolutely know.

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Bax_Cadarn t1_j97cf64 wrote

I'm studying for a big exam and basically every disease, restrictive or obturative, lowers DLCO lol. (Barring alveolar hemorrhage). Not just COPD or smoking-related diseases like DIP.

By identifying cells from BF or EBUS or biopsies, You mean like looking for macrofages loaded with soot?

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Snoo16319 t1_j97g3yn wrote

Lung doc here. Not all obstruction reduces DLCO, DLCO is traditionally preserved in non-remodeled asthma.

That said, as a lung cancer researcher, KRAS mutation is much much more common in those who have smoked (not exclusive though). In modern practice, we are doing more assessment of tumor mutational burden and TMB is a lot higher in those who have smoked. Lastly, some subtypes, namely small cell and squamous cell, are almost unheard of in those who have never smoked.

Establishing causation in science is hard, and we observe changes correlated with tobacco use, but as they say, correlation and causation are not the same. We know epidemiologically and through cell and animal models the effects of tobacco smoke on DNA and cell growth, but in an individual, it would be close to impossible to establish exact causation.

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sirtuinpeach t1_j9acjfm wrote

I disagree with the people saying no here. Thanks to genome sequencing and tumour genome sequencing, we can definitely start chipping away at the cause of some cancers. Have a look at mutational signatures in human cancer on Google scholar. Some carcinogens can leave distinct signatures in tumour DNA, allowing determination of cause in some cases. Cigarette smoking is a good example of something that leaves a unique mutational signature. It’s a super interesting topic. There’s a great paper by Alexandrov et al (2020) in Nature.

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sirtuinpeach t1_j9acwzd wrote

I think the tricky nuance with determining what has caused someone’s cancer is that cancer emerges after a few pre-cancerous mutations rather than just the one - kind of like a slippery slope mutation cascade that increases the likelihood of full blown malignant cancer by massive amounts with each mutation. So whilst smoking might cause one of those mutations, it’ll take a few more to become malignant! And then another few more to become metastatic cancer, the biggest killer

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Thugluvdoc t1_j9as8po wrote

Sort of. Over the long term, they can do retrospective research (not very good data but still data) and prospective studies. Retrospectively they can survey or see the data of every person who smokes, vapes, and does both. They can do the same prospectively. Then they can see what cancers are more prevalent in group 1 2 or 3. For example, smokers got cancer A 5x more, vapers got cancer B 3x more, and both smokers got cancer C 2x more you can conclude that cig cause more cancer A, vapes cause more cancer B, and so forth. It’s just time and data. Don’t forget causation isn’t always a direct correlation. The best example is ashtrays. People with ashtrays in their homes have much higher lung cancer rates - is it the ashtrays causing cancer? No it’s the smoking. So sometimes you have to step back and ask if there is truly a direct causation between what you are studying and the outcome

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sommerniks t1_j99imxo wrote

Sometimes. If you have an HPV related cervical cancer and claim you're a virgin they're not really going to believe it.

Also, about the smoking: lying about it won't always work because they have noses and you're going to be wanting to take cigarette breaks during your hospital stay. If you quit smoking a while ago you're likely to mention it because quitting is a positive thing.

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Norklander t1_j99m0uh wrote

HPV can be transmitted via any skin to skin contact, so it’s not correct to assume high risk strain HPV related cancers are all related to sexual contact, however most are.

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sommerniks t1_j9a5n62 wrote

Close skin to skin contact of the genital area, it says, and the risk from hand-to-genital transmission is extremely low. How much of a virgin are you if you've had everything but penetration?

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Norklander t1_j9biiaf wrote

Skin to skin contact, including oral sex can transfer HPV virus. In some cultures/counties the definition of a virgin means no vaginal/penile penetrative sex, therefore it’s important in the context of cervical cancer not to equate absence of the above with zero risk of cervical cancer.

For example in Turkey when the Erdogan government rolled out HPV primary testing for cervical cancer screening (in 2014) the message got hijacked by right wing religious parties saying the infection was only sexually transmitted (mainly in the SE Turkey region), and that an HPV positive result meant the person had an STI. Result was uptake was low and cervical pre-cancers were missed as women were scared and men scared of being stigmatised or accused as a result.

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sommerniks t1_j9bklup wrote

Yeah, I know and the strict Christians refused vaccination based on the virgin principle too.

But still the doctors I know would want some explanation about that virginity, and consider oral sex 'sexually active' for example.

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Norklander t1_j9blrk1 wrote

Yes it’s a tricky subject but the consensus among clinicians and epidemiologists is that HPV is not an STI and shouldn’t be treated as such, but it doesn’t stop people deliberately confusing it for their own ends which is unfortunate.

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jawshoeaw t1_j99lvnv wrote

Usually no. There are a few very rare cancers like mesothelioma that are only caused by one thing (asbestos) or the more common squamous cell carcinoma of the cervix which is almost always caused by HPV . But usually we have no idea because cancer is an accumulation of errors. One error could be a diesel truck that spewed exhaust in your face, another error could be a cosmic ray or a random event or a chemical in the water you drank

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