4 ms·

Here's a curve that represents the rate of cancer diagnosis by age in the UK. http://www.cancerresearchuk.org/cancer-info/cancerstats/incidence/age/#Cancer htt

Here's a curve that represents the rate of cancer diagnosis by age in the UK. http://www.cancerresearchuk.org/cancer-info/cancerstats/incidence/age/#Cancer http://www.cancerresearchuk.org/cancer-info/cancerstats/inci... If cancer were only about a mutation happening randomly, you'd expect the curve to actually slope downwards, like an exponential distribution. But maybe cancer requires several mutations to happen in a row, which would suggest an Erlang distribution of which we only see the beginning of the hump. 20 mutations give a very good curve fit (1). An alternative hypothesis is senescence. Maybe the mutation rate itself increases with age, or maybe the immune system isn't as able to nip cancerous growths in the bud. This is important! Whenever the impact of a disease doesn't follow a chi squared or exponential distribution, it suggests two ways to fight the disease. Directly target the disease itself, or target the process which over time makes us more susceptible to it. (1) warning, back of the envelope, there are plenty of other effects to account

revelation 12y ago
That looks like a perfectly fine exponential distribution.
- murbard2 12y ago
  No it doesn't. The exponential distribution p.d.f. is decreasing. http://en.wikipedia.org/wiki/Exponential_distribution#mediaviewer/File:Exponential_pdf.svg http://en.wikipedia.org/wiki/Exponential_distribution#mediav...
  - revelation 12y ago
    But that's not what we are interested in, no? Nobody asks "whats the probability that you'll get cancer at precisely age x", they ask "what's the probabiblity that you'll have cancer by age x". I mean, we often can't even determine at what precise age the cancer developed. That's a problem for the PDF, not so much the CDF.
    - murbard2 12y ago
      The graph I linked to plots the PDF. It's not exponential. It indicates something is getting worse over time.
toufka 12y ago
We know quite clearly that cancer is (generally) caused by a set of mutations - not necessarily in an order, but some orders are not successful. There are four or five genes which keep social order amongst the other genes. If you silence all of these, you get cancer. Cells that deviate from what they're supposed to do are either (in order), repaired, silenced, voluntarily commit suicide, or are killed. There are proteins (genes) that are the final judges for each of these processes - and have 'go, no-go' power. Only if all of these judges are killed do you get a cell that can do anything it wants - like replicate uncontrollably to the detriment of the host ('cancer'). Thus the statistics of getting cancer roughly follow the idea that you have to get random DNA modifications of those exact 5 genes, in a single cell. Lots of things can increase your random modification rate (UV, smoke, radiation, etc). Some of these things correlate though - and again, what hurts one cell, might hurt its neighbor just as bad. They're not entirely independent events. For example, losing your DNA repair machinery (this is what HPV does - it silences your DNA repair machinery) amps up the baseline mutation rate and makes further mutations more likely (dependent correlations then arise). The Brca gene that has caused so much controversy in patent law (whether a test for its existence could be patented) and indicates whether a person might or might be susceptible to breast cancer, is the master repair technician of the cell. In people who have this gene in working order, the Brca gene signs off on whether the cell is in need of repair. But if the Brca is not it working order, cells that are in need of repair might not get it, and instead are allowed to more freely operate under non-optimal internal conditions. If you are missing or have a mutated version of Brca, you are missing one of the checkpoint processes. So again, we quite clearly know of a handful of genes which do most of the master regulation of a cell's job - and if these jobs go unfulfilled - by having their blueprints be damaged by the environment - you have fewer and fewer mechanisms to prevent that single cell from runaway growth.

revelation 12y ago

That looks like a perfectly fine exponential distribution.

murbard2 12y ago
No it doesn't. The exponential distribution p.d.f. is decreasing. http://en.wikipedia.org/wiki/Exponential_distribution#mediaviewer/File:Exponential_pdf.svg http://en.wikipedia.org/wiki/Exponential_distribution#mediav...
- revelation 12y ago
  But that's not what we are interested in, no? Nobody asks "whats the probability that you'll get cancer at precisely age x", they ask "what's the probabiblity that you'll have cancer by age x". I mean, we often can't even determine at what precise age the cancer developed. That's a problem for the PDF, not so much the CDF.
  - murbard2 12y ago
    The graph I linked to plots the PDF. It's not exponential. It indicates something is getting worse over time.

toufka 12y ago

We know quite clearly that cancer is (generally) caused by a set of mutations - not necessarily in an order, but some orders are not successful. There are four or five genes which keep social order amongst the other genes. If you silence all of these, you get cancer. Cells that deviate from what they're supposed to do are either (in order), repaired, silenced, voluntarily commit suicide, or are killed. There are proteins (genes) that are the final judges for each of these processes - and have 'go, no-go' power. Only if all of these judges are killed do you get a cell that can do anything it wants - like replicate uncontrollably to the detriment of the host ('cancer'). Thus the statistics of getting cancer roughly follow the idea that you have to get random DNA modifications of those exact 5 genes, in a single cell. Lots of things can increase your random modification rate (UV, smoke, radiation, etc). Some of these things correlate though - and again, what hurts one cell, might hurt its neighbor just as bad. They're not entirely independent events. For example, losing your DNA repair machinery (this is what HPV does - it silences your DNA repair machinery) amps up the baseline mutation rate and makes further mutations more likely (dependent correlations then arise). The Brca gene that has caused so much controversy in patent law (whether a test for its existence could be patented) and indicates whether a person might or might be susceptible to breast cancer, is the master repair technician of the cell. In people who have this gene in working order, the Brca gene signs off on whether the cell is in need of repair. But if the Brca is not it working order, cells that are in need of repair might not get it, and instead are allowed to more freely operate under non-optimal internal conditions. If you are missing or have a mutated version of Brca, you are missing one of the checkpoint processes. So again, we quite clearly know of a handful of genes which do most of the master regulation of a cell's job - and if these jobs go unfulfilled - by having their blueprints be damaged by the environment - you have fewer and fewer mechanisms to prevent that single cell from runaway growth.