3 ms·

I'm pretty confused by the term 'luck' in these papers. Surely 'random mutation' is exactly how cancer propagates in all cases? Risk factors coexist with 'luck'

by _xander 12y ago

I'm pretty confused by the term 'luck' in these papers. Surely 'random mutation' is exactly how cancer propagates in all cases? Risk factors coexist with 'luck'. The chance of suffering a cancerous mutation is like rolling a dice, and risk factors are the equivalent of the number of dice being rolled. It's not a question of 'OR', it's a question of 'AND'. E.g.: You're a smoker who develops lung cancer: you are 'unlucky' in the sense you suffered a random mutation AND also 'responsible' because you smoke, which is a primary risk factor.

gms7777 12y ago
I haven't read the Vogelstein paper yet, but from the abstract it seems that when its talking about 'luck', its talking about errors in DNA replication. The rate of these errors is pretty constant in healthy cells (about 1 per duplication), so its pretty much a matter of luck whether you acquire a mutation in a place that matters or a place that doesn't, and it doesn't really matter who you are or where you are. He seems to be contrasting this to other mechanisms that cause mutations, like chemicals, radiation, or viruses. Sure there is 'luck' involved at the individual level once you've been exposed, but the point is if you reduce exposure across the population, you reduce incidence rates. With DNA replication, there isn't anything you can do to reduce incidence rates.
mikeechoalpha 12y ago
Wow, this is so satisfying. I was wanting to comment something along these lines, but couldn't have put it any better.
Confusion 12y ago
The question is: would the random mutation have occurred and have resulted in cancer anyway for most of those engaging in 'risky' behavior? Suppose only breast cancer (in women), prostate cancer (in men) and lung cancer (in both genders) existed. Suppose further that breast and prostate cancer account for 60% of all cancers and that smoking doubles the chance of lung cancer, but doesn't influence the chances for breast or prostate cancer. For any individual cancer patient, the chance that they were 'unlucky' would be much larger than the chance that their behavior was relevant to their cancer. This is true even for those that smoke. Especially for those that get breast or prostate cancer, but even for lung cancer it would be 50/50.

by _xander 12y ago

gms7777 12y ago

I haven't read the Vogelstein paper yet, but from the abstract it seems that when its talking about 'luck', its talking about errors in DNA replication. The rate of these errors is pretty constant in healthy cells (about 1 per duplication), so its pretty much a matter of luck whether you acquire a mutation in a place that matters or a place that doesn't, and it doesn't really matter who you are or where you are. He seems to be contrasting this to other mechanisms that cause mutations, like chemicals, radiation, or viruses. Sure there is 'luck' involved at the individual level once you've been exposed, but the point is if you reduce exposure across the population, you reduce incidence rates. With DNA replication, there isn't anything you can do to reduce incidence rates.

mikeechoalpha 12y ago

Wow, this is so satisfying. I was wanting to comment something along these lines, but couldn't have put it any better.

Confusion 12y ago

The question is: would the random mutation have occurred and have resulted in cancer anyway for most of those engaging in 'risky' behavior? Suppose only breast cancer (in women), prostate cancer (in men) and lung cancer (in both genders) existed. Suppose further that breast and prostate cancer account for 60% of all cancers and that smoking doubles the chance of lung cancer, but doesn't influence the chances for breast or prostate cancer. For any individual cancer patient, the chance that they were 'unlucky' would be much larger than the chance that their behavior was relevant to their cancer. This is true even for those that smoke. Especially for those that get breast or prostate cancer, but even for lung cancer it would be 50/50.