
Bad luck, bad journalism and cancer rates - auton1
http://www.theguardian.com/science/grrlscientist/2015/jan/02/bad-luck-bad-journalism-and-cancer-rates
======
waldrews
Oy vey. Statistician/statistical geneticist here. The second article is too
harsh on the first. The point is subtle and hard to express: carcinogens set
the odds, but importance of the part of the risk due to "biological luck," the
part that comes from the mutation chain, means whether you individually are
affected is random in a way that makes it hard to bother protecting yourself.

Let's say (arbitrary numbers) having poisonium in the food supply increases
the lifetime population rate of cancer of the thingamajig from 0.11% to 0.12%.
In the US, banning poisonium will save 300 million * (0.12%-0.11%) = 30,000
people, very predictable and important. However, if you personally go on a
poisonium-free diet, you decrease your personal risk by 0.01%. You chances go
from about 1 in 1000 to about 1 in 1000... so maybe if it involves any effort,
you should spend your time doing something else to improve your health.

It's different if the carcinogens targeted specific vulnerable groups. If
there was one gene that makes you instantly get cancer at the first whiff of
poisonium, we would screen everyone for that gene. The difference between the
0.12 and 0.11 would be due that gene. Everyone with that gene would be put on
poisonium-free diets. Everyone else can eat all the poisonium they want, and
would still have 0.11 risk. (This is more or less the situation with the
active ingredient in aspartame sweetener, though the disease is not cancer)

I don't like the use of the word "luck" in these descriptions, since both
genetic and mutation chain randomness are a kind of luck. Also, the studies
give quality numbers across many cancers, but the basic concept has been a
mainstream model of cancer risk for a long time.

~~~
Retric
I think your misrepresenting the data.

Absolutely nothing about the data collected related to different human
populations just different types of tissue.

Further, I don't see anything that relates to % of biomass of the tissue just
total cell divisions. Presumably the skin, lungs, a digestive track tissues
are at high risks because they compromise a lot of tissue, it divides rapidly,
and it's not protected from environmental factors ex: sunlight/smoking/spicy
food. However, I suspect the paper digs into things a little further to
account for such factors.

~~~
waldrews
Yeah, I'm talking about the different populations thing to illustrate an
extreme example about the 'luck' concept. It's not directly related to the
study.

Not sure I understand the % biomass issue. The tissues you're referring to -
epithelial - are the ones doing the bulk of the cell division in adults, and
the ones where you'd typically get the (early stage) cancers. Something like
smoking increases your risk in two ways. You get a higher mutation rate
(chemicals enter your cells and mess with DNA replication). You also increase
the number of 'lung cells' you need to clean out and replace, causing more
cell division. Obesity (and size in general) has a direct theoretical effect:
more cells = more opportunities to divide = more risk events. Caloric
restriction presumably is the opposite of that: do nothing and eat nothing,
don't have your cells get replaced, and you reduce the number of risk events.

I think the deeper question in cancer math, if you get the single-gene level
biologists and population level statisticians to talk to each other, is how
much of the cancer is due to mechanics (number of cells, division counts) that
are out of our control, mechanics that we can affect, genetics that are out of
our control, and how much is genetics that are fragile but susceptible to
prevention and early treatment. That's the sweetspot; that's what we
ultimately want to find - genetic markers of things that are going to break
but can be patched or protected or fixed.

That's why we want accurate models of risk - in different kinds of tissues -
in the first place.

~~~
Retric
"Not sure I understand the % biomass issue."

It seems like more cells = more risks of mutation = more risk of cancer. So, I
would presume it's something that needs to be accounted for in their model.

However, based on the wording that seems to be total cell divisions and I
don't know enough about rates of cell division or cancer to tell from that
chart. In the end a gall bladder weighs less than 1/4th of a pound where the
small intestine is ~3.5 pounds so it hardly seems like they can just ignore
it.

Though, if it's really just cell divisions and not organ weight that matters
then that's a much stronger finding IMO.

PS: And no I am not paying 20$ to read the actual article. Though if it's free
somewhere I would like to read it.

~~~
ggrothendieck
The fact that species with more cells don't get more cancer is known as Peto's
paradox. Perhaps it is also true at the tissue level. See
[http://en.wikipedia.org/wiki/Peto%27s_paradox](http://en.wikipedia.org/wiki/Peto%27s_paradox)

------
Gatsky
I was quite surprised to find this in one of the most prestigious journals in
the world. Vogelstein is one of the biggest names in cancer research, and no
doubt that was the most important factor in its publication.

Some problems: 1\. They leave out breast cancer and prostate cancer, two of
the most common cancers out there. Most of the dots on their plot relate to a
tiny proportion of cancers that people get. Furthermore, breast cancer has a
very low mutation rate, which also casts doubt on their hypothesis about
accummulation of somatic mutations on stem cells.

2\. I ran their data using just the number of stem cells and the number of
cells versus incidence. The correlations are still good, about 0.5 for just
cell mass and 0.67 for number of stem cells. It's hardly a revelation that a
larger more cellular organ is more likely to get cancer.

3\. For glioblastoma, a type of brain tumour, their data says that there are 0
stem cell divisions, because it is thought there is no cell renewal in the
brain (which isn't even true, but anyway). This contradicts the whole
hypothesis, but they still include it in there.

4\. The lifetime incidence of various cancers is age dependent. For example
sarcomas almost always occur in the young, medulloblastoma is vanishingly rare
in the elderly, testicular cancer occurs in young men. Their hypothesis
ignores all this, because their model only allows for the acquisition of
mutations over time, which should give a unimodal relationship between age and
cancer incidence.

5\. There are cancers that have almost no mutations. Gene copy number changes
are just as important if not more so than mutations. There is very little
evidence that copy number changes accumulate over time in stem cells in a
random fashion required by this model.

I don't think this warrants much attention in the end. This can join the
100,000 other unverified (or unverifiable correlations) in the cancer
literature.

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therealdrag0
I want to reiterate the articles recommendation of the book "Bad Science" by
Ben Goldacre [0]. I learned a lot from it and found it enjoyable--and it's
available in Audiobook form.

[0] [http://smile.amazon.com/Bad-Science-Quacks-Pharma-
Flacks/dp/...](http://smile.amazon.com/Bad-Science-Quacks-Pharma-
Flacks/dp/0865479186/)

------
toufka
Here's the deal - we know it's 'chance' (not really luck) which part of your
DNA is damaged by any given environmental effect. However, some DNA is more
important than others. In general, a little damage is not a problem and is
easily 'taken care of' by the cell which caries that DNA - either by literally
repairing the DNA, silencing that DNA's function, killing itself, or asking
other cells to help kill it.

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. Chance has it's role in the roll of dice
for which DNA gets damaged, but all the other parameters can be changed too -
how many sided the dice are, how often the dice get rolled, and whether all
the cells in the same tissue have correlated dice-rolls.

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.

~~~
fideloper
Would I be incorrect in saying that cells can replicate imperfectly without
being cancer? Isn't that aging?

~~~
toufka
You would be correct. Errors are not the same as cancer.

Cancer is generally a cell that can replicate uncontrollably on its own (most
cells would die if extracted from their very particular environment). Your
body has trillions of cells. Many have mistakes, errors and other issues. Most
of the trillions of times the errors are very minor and in no way cause
uncontrollable cancer - merely a less efficient cell. Only a countable number
of times in trillions of cells dividing every day for 80 years are those
errors precisely of the kind that would permit uncontrollable replication -
cancer.

Aging is different yet. Copying of dna has a Turing issue. It's really hard to
copy the end of a Turing tape when you have to hold that tape to copy it. So
dna keeps roughly 60 replications worth of dead space at the end of each
strand of dna. So even if the replication machinery drops a page or two at the
back of the book full of blueprints, it doesn't matter so much. But after 60
divisions or so (a human's lifespan), the replication starts eating into the
actual useful blueprints - dramatically increasing the chance of failing to
copy an essential gene. These blank pages are called 'telomeres' and the Nobel
prize was recently awarded for their discovery.

------
vasilipupkin
the original paper is kind of confusing itself. Why would they essentially do
a 1 variable regression? why not do a multiple regression with lifetime cancer
risk as y variable and both number of cell divisions and smoking as x
variables?

------
leg100
What's the difference between bad luck and "we just don't know"?

~~~
UhUhUhUh
Exactly. The same old debate between statistical truth and deterministic
uncertainty. What bothers me is that, meanwhile, the many people who have
tried to get funding for years or even generations to study deep, complex
mechanisms involved in DNA replication (on histones for example) didn't get
much. Of course replication will eventually, on large numbers, begin to fail.
Microprocessors do too. But would we say that when instructions get
contaminated it's bad luck?

------
ekianjo
Wait, is this an article from the Guardian making fun of their own article on
the same study earlier on ? See
[http://www.theguardian.com/society/2015/jan/01/two-thirds-
ca...](http://www.theguardian.com/society/2015/jan/01/two-thirds-cancer-cases-
caused-bad-luck-lifestyle-genes) ? If that's the case, that's a novel way of
doing journalism: publish crap first, then sell more paper by doing a critique
of your crap.

~~~
arrrg
Why do you assert that there is malice involved? That just makes no sense.
What’s with this reflexive impulse to always, always, always loudly proclaim
malice?

I just don’t get where this weird worldview comes from. If there is no malice
involved then this is not a big deal. Wow, people working for the same
publication nevertheless criticise each other. Oh my god, what a concept!

~~~
spuz
I don't understand. What malice exactly is being asserted in the parent
comment?

~~~
therealdrag0
Probably the idea of conspiring to intentionally publishing something to later
criticize it instead of publishing the correct thing first.

------
dang
Also
[https://news.ycombinator.com/item?id=8827666](https://news.ycombinator.com/item?id=8827666).

------
termostaatti
Naturally the way one lives has an impact whether potentially he/she will get
cancer. Smoking, drinking, eating certain types of food (manufactured wrong)
etc. all have direct relation on cancer. It's never just _luck_ who happens to
get these horrible diseases.

~~~
hueving
Please provide evidence when you say these kinds of things. Causation is
rarely as intuitive as you would like to believe.

~~~
termostaatti
Well, carcinogen is one those things that has been known for decades causing
cancer. And yes, human-being can make the difference whether they have those
unnatural carcinogens or not.

~~~
michaelhoffman
There are plenty of "natural" carcinogens too. Avoiding carcinogens may reduce
your cancer risk, restricting yourself to things that are "natural" won't.

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MisterMashable
Whatever the official cause of cancer it will never be food additives,
processed or poor quality foods, prescription drugs, air pollution,
contaminants in the water supply, contaminated vaccines (I'm a believer in
vaccines so don't go there!), new car smells, pesticide residues in food and
clothing, fire retardant chemicals, xenoestrogens, secondary cancers caused by
chemotherapy or radiation... it will just be bad luck.

