
Most types of cancer not due to “bad luck” [pdf] - wslh
http://www.iarc.fr/en/media-centre/pr/2015/pdfs/pr231_E.pdf
======
carbocation
This document is both a political document and, to a lesser extent, a
scientific one.

On the political front, the document encourages people to reject that cancer
predilection is stochastic and to encourage the continued study of cancer.

The scientific component attempts to provide an underpinning to the political
goal. It uses a handful of epidemiological examples, such as the climbing
incidence of colorectal cancer in Japan over a genetically-insignificant
timescale (which suggests an environmental factor at play).

The article fails to support its headline ('Most types of cancer not due to
"bad luck"') through any scientific instrument. While its policy goal (the
continued pursuit of the causes of cancer) is reasonable, nobody is saying
that we now know that cancer is predominantly caused by bad luck so we should
stop studying it (certainly not Vogelstein, whose career is built on the study
of cancer).

Overall, it's not clear to me why this was published.

~~~
i000
The cancer research and cancer epidemiology communities do not really talk to
each other (as a cancer researcher for many years I have never been to an
epidemiology seminar despite working in a 'cancer center'). So it is really a
fight for money and mind influence. Most cancer researchers lean towards drugs
targeting molecular mechanisms of cancer, cancer epidemiologists, on the other
hand, aim for political decisions that combat environmental factors. Where
should most money go? what should be discussed in the media?

Vogelstein proposes a simple model that explains a lot of data. Sure, the
implications are bleak, but the scientists I talked to were not really
surprised that it finally got out.

~~~
phkahler
>> as a cancer researcher...

Iodine. Have you looked into it? The abstracts over on nih.gov are pretty
interesting - google for "iodine cancer nih" without quotes. I'm curious what
a cancer researcher has to say. Mostly I'm interested in weather your peer
group has even looked at this.

~~~
i000
> your peer group has even looked at this.

I think it will help most if I explain the incentives for scientists (at least
in the US). From their first day in the lab scientists are rewarded most for
generating data and making discoveries. The more novel and paradigm shifting
the discovery the better - as it opens the door to high-impact publications
and future research money. But "extraordinary claims require extraordinary
evidence" and the more unexpected the finding the more difficult it is to
convince your peers and get it published.

Somewhat idealistically, this has two consequences for a good lead scientist:
1) hew will guide his lab to explore the unexplored 2) and subject the most
novel and promising findings to the most stringent experimental verification.

So the answer to your direct question - yes probably someone somewhere tried
to test the iodine-breast cancer hypothesis, but since it is not a major topic
in breast cancer research the experiments have probably failed and were not
published and thus independently replicated

------
calinet6
This shows a severe misunderstanding of statistics.

The original paper (here:
[http://www.sciencemag.org/content/347/6217/78.abstract](http://www.sciencemag.org/content/347/6217/78.abstract)
\-- the abstract is enough to deduce the conclusion) is a simple statistical
analysis of mutation probability in certain cell types. It's basically saying
that many cancers are not necessarily influenced by external factors and can
be predicted by nothing more than the number of cell divisions and the
probability of DNA mutation compounded.

That, in itself, is a _fascinating_ scientific result. Arguing against the
statistics here is probably not a good idea, unless there was a serious error
in the math or an order of magnitude error in the probability of mutation.
Certainly there are other possibilities of error in the data or methodology.

But the article in opposition (OP) is doing something odd that doesn't appear
to be a scientific argument: it's railing against the language and the
implications of the very concept of statistical analysis applied to the
problem. It's assuming that because we discovered that, perhaps, cancer has a
certain probability of occurring independent of external factors, that it will
somehow slow research or cause us to throw up our hands and give up on
prevention strategies or research.

I don't think that's the case. Rather than understanding the absolutely
fascinating statistical analysis here, the OP article comes across as
reactionary and unscientific.

Assuming the data is sound, the statistical analysis is profound. Most often,
statistics such as that are profoundly misunderstood as well: people have an
incredible capacity for attribution bias and data disbelief. This simply
underscores the need for a better education in basic statistics as well as
science across the board.

~~~
orting
A specific critique raised in the press release from IARC is that the study
has an

"emphasis on very rare cancers (e.g. osteosarcoma, medulloblastoma) that
together make only a small contribution to the total cancer burden."

and that it

"excludes [...] common cancers for which incidence differs substantially
between populations and over time."

So it sounds like the generalization hinted at in the abstract shows a bigger
misunderstanding of statistics than any in the press release. Would be nice if
the paper was not paywalled, so we could actually read it.

~~~
FrojoS
I put the full paper in pastebin:
[http://pastebin.com/GH1ZY8Zx](http://pastebin.com/GH1ZY8Zx)

Didnt read it, so not sure if its sufficiently understandable without the
figures. Prob not.

~~~
smtddr
What's HN's stance on posting a paywalled article to pastebin like this? If I
were to guess, I'd think this to be frowned upon.

~~~
matznerd
I frown upon it because I prefer the PDF :P

~~~
LispShmisp
Here you go: [http://www.uvm.edu/~cdanfort/csc-reading-group/tomasetti-
sci...](http://www.uvm.edu/~cdanfort/csc-reading-group/tomasetti-
science-2015.pdf)

------
_xander
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
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.

------
lbhnact
It bears pointing out some inaccuracy in language here, notably that 'types'
and 'cases' are not the same thing.

Most 'types' of cancer are unequivocally about bad luck; nearly any cell line
in your body can develop overproliferative mutations. There are hundreds of
'types' of cancer.

'Cases' and deaths from cancer are, globally and in the US, more
environmentally influenced, because of the huge impact of smoking on lung and
colorectal cancer incidence and mortality in particular.

------
mark_l_watson
Great advise. There is nothing we can do about our "cancer good/bad luck" but
there is a lot we can do to control life style issues.

This is just my opinion, but I think all of the following probably help: try
to have much less stress in your life; plenty of exercise; prefer organic food
if available; avoid deep fried food; go light on barbecuing, as tasty as it
is; eat lots of and a wide variety of green vegetables.

------
Shinkei
Physician here. I think I can provide some clarification for what is going on
here. I just read the article the WHO is addressing and this is a line from
the final paragraph:

 _Our analysis shows that stochastic effects associated with DNA replication
contribute in a substantial way to human cancer incidence in the United
States._

First, the terminology is important to understand. In medicine, "stochastic"
is in contrast to "deterministic" which describe the occurences of pathology
based on a risk factor. In a "stochastic" model, if you receive 10 severe sun
burns then your chances of getting a skin cancer go up over someone who only
received 1 severe sun burn, but are by no means certain or even that your
cancer will be more severe... simply an increase in probability. In a
"deterministic" model, if you receive 5 Grays of radiation then you will have
less severe symptoms than someone who received 50 Grays of radiation and for
the most part, your symptoms will be certain and predictable.

Now you need to have one element of cancer biology under your belt:

[http://en.wikipedia.org/wiki/Carcinogenesis](http://en.wikipedia.org/wiki/Carcinogenesis)

This basically says that as cells divide, errors are propagated through their
progeny until there is a proverbial 'straw that breaks the camel's back' and
the cell becomes cancerous.

In summary, that line from the final paragraph is basically saying that cells
that divide more rapidly in the human body are more likely to become cancer.
Well, yeah of course!

We have known this for a long time but what this paper did is sort cancers
into two groups, one that is primarily stochastic and one that is primarily
deterministic. The result _appears_ impressive because they have a lot of
cancers on the stochastic side... stating that their incidence is more
predicted by cell division rather than the deterministic, preventable factors.

But as the WHO correctly stated, they are incorrectly analyzing this data as
described in this paragraph:

 _These include the emphasis on very rare cancers (e.g. osteosarcoma,
medulloblastoma) that together make only a small contribution to the total
cancer burden. The report also excludes, because of the lack of data, common
cancers for which incidence differs substantially between populations and over
time. The latter category includes some of the most frequent cancers
worldwide, for example those of the stomach, cervix, and breast, each known to
be associated with infections or lifestyle and environmental factors._

The cancers grouped into the stochastic side overall make up a tiny percentage
of all cancers and so by number/%/incidence, the deterministic side would be
enormous if graphed appropriately. For example, their most 'stochastic' cancer
is pancreatic islet cell which only has 2500 cases/year in the US vs their
'lung smokers' cancer which has >220,000 cases/year.

I mean they seem almost willfully blind to their incorrect conclusion.
Environmental factors are HUGE and the cancers caused independent of those
would not benefit from screening and environmental risk reduction--a fact we
already know!

As a last note, the 'most' deterministic cancers--inherited types--have to be
agressively treated with screening, prophylactic measures and environmental
exposure risk reduction, etc. You can read about a couple of the deterministic
cancers they mention in this paper:

[http://en.wikipedia.org/wiki/Familial_adenomatous_polyposis](http://en.wikipedia.org/wiki/Familial_adenomatous_polyposis)

[http://en.wikipedia.org/wiki/Lynch_syndrome](http://en.wikipedia.org/wiki/Lynch_syndrome)

~~~
mirimir
This is the key point. Tomasetti and Vogelstein (2015) arguably demonstrated
that most types of cancer are primarily stochastic. But it's the primarily
deterministic types of cancer that account for most morbidity and mortality.

------
fspeech
The variation among geographic locations is interesting. On the other hand the
rise in the rate of colorectal cancer in Japan may simply be due to a rise in
cancer screening. Do Japanese die more often from colorectal cancers? For an
example of why this is relevant, over 80% of men in their eighties may have
prostate cancer yet the lifetime risk of dying from it is only 3% for a 50
year old man in the US (see
[http://ije.oxfordjournals.org/content/36/2/278.full](http://ije.oxfordjournals.org/content/36/2/278.full)
). So if we improve screening of prostate cancer we may find a lot more cases
even though men's risk of dying from it is unchanged.

~~~
fspeech
"A recent autopsy study reported on 314 African American and 211 Caucasian
(sic) men aged 20–80 years who died of trauma in Detroit, USA. Microscopic
evaluation in each case was based on 10–14 whole-mount step sections that were
2–3 mm thick.4 This study demonstrated a high prevalence of prostate cancer
that increased progressively with advancing age and was similar at all ages in
African American compared with Caucasian men (around 10%, 30%, 40%, 45%, 70%
and 80% in the 3rd, 4th, 5th, 6th, 7th and 8th decades, respectively). When
this ubiquity of microscopic prostate cancer is placed in the context of
lifetime risks of clinical or fatal prostate cancer (about 10% and 3%,
respectively for a man aged 50 years in the USA),5 these data indicate that
local or distal progression of early cancer is far from inevitable within a
man's lifetime. Put another way, only a minority of prostate tumours are
highly aggressive and life-threatening, while the majority are slow-growing
and indolent."

------
athenot
A piece of data that appears to corroborate this article was recently on HN.
It concerned a Greek island where people have unusual long life[0], and
followed a man who was diagnosed in the US by 9 doctors with terminal
cancer... only to survive them all from his island where it is believed
several lifestyle factors play important roles in longevity (and cancer
prevention/recovery for this man).

[0] [http://www.nytimes.com/2012/10/28/magazine/the-island-
where-...](http://www.nytimes.com/2012/10/28/magazine/the-island-where-people-
forget-to-die.html?pagewanted=all&_r=0)

------
jkot
> _For many cancers, the authors argue for a greater focus on the early
> detection of the disease rather than on prevention of its occurrence. If
> misinterpreted, this position could have serious negative consequences from
> both cancer research and public health perspectives._

> _In principle ... nearly half of all cancer cases worldwide can be
> prevented_

I am not sure what to take from this article. Lung cancer prevention is
already in progress. At the same time prostate cancer has even higher
mortality (for non smokers) and preventive checks are not even covered by most
insurance companies.

~~~
regularfry
Is it a myth that prostate cancer is something you die with, rather than die
of?

~~~
jkot
I dont know. But in Europe preventive checks are highly recommended (and
covered).

~~~
underyx
Where in Europe?

~~~
nazgob
Germany, Sweden, Poland, probably most of EU.

------
Gatsky
This official statement is rather odd as others have pointed out. Anyway, the
biggest problem with the original paper is that they leave out breast and
prostate cancer, the two most common cancers. Maybe these would support their
hypothesis, but they leave them out and they don't really explain why. It's
probably because we aren't sure what the true incidence is, due to
ascertainment bias from increased screening. Whenever I read a broad ranging
conclusion in life sciences research, I remind myself to stick <Except when it
isn't> on the end (eg Most cancer is due to bad luck - except when it isn't.)

The paper also technically sets out to explain why cancer incidence varies
between different tissues. An analogy is correlating the average temperature
with distance from the equator. It is clear that most of the difference in the
mean temperature of Equador compared to Iceland is explained by distance from
the equator. You can create categories like number of days with rain, number
of days with a temperature > 30 degrees C, and each of these values will be
highly correlated with distance from the equator. But it does not follow that
this strong correlation means that there are hardly any environmental
influences on the temperature in St Petersburg tomorrow, and that we can fire
all the meteorologists.

(Disclaimer for what follows: I do life sciences research, so I may have an
overly pristine view about physics.)

The really interesting thing about all this I think is the collision of
maths/physics/engineering and life sciences! Vogelstein wrote this paper with
a mathematician. They basically did a back of the envelope calculation, an
approach that is much favoured by engineers but completely alien to life
science researchers. These simple calculations are useful because in the
physics/engineering paradigm, abstractions are incredibly powerful and non-
local. For example, many important physical laws that apply equally across
many orders of magnitude, can be derived from thinking about falling apples or
billiard balls. Paul Dirac predicted the positron by simply exploring other
possible solutions to an equation! To me, this is an extraordinary and winning
moment for quantum physics, where the theory is so powerful, that it can drag
us screaming towards completely unintuitive and otherwise inaccessible
conclusions. To a biologist, this kind of thing is ridiculous and alien. The
same abstractive power is almost completely absent, and both experimental and
theoretical models are extremely limited.

There are many reasons for this. You could argue that biology is not amenable
to the often time-invariant abstractions so useful in the other sciences. Or
perhaps biologists aren't trained to think that way. In any case, it is
interesting to watch when an engineer encounters biology, and this paper is an
example. I am still not sure whether we need more engineers in biology or not?

I think it is abundantly clear though that breakthroughs in biology don't come
from professors having epiphanies while walking amongst the pine cones on a
cloudy autumn day. Human intuition alone is failing to get us very far in
biology. We need a paradigm that can deal efficiently with uncertainty,
incomplete yet massive data, noise, simulation of highly parallel processes on
long time scales, causality in networks of highly correlated actors etc - I
hope that some future melding of computer science, biology and staggering
computational resources will give us more useful ways to investigate life.

------
known
Cancer is like Nuclear FUSION;

------
StavrosK
Jeez, make up your mind, science!

~~~
SquareWheel
It's not as simple as that. Most "indecisiveness" that appears to come from
science is from different studies being taken out of context, or poor media
reporting. Most wild claims you see aren't from the researchers themselves.

See Steven Novella's recent blog post on this subject.

[http://theness.com/neurologicablog/index.php/scott-adams-
on-...](http://theness.com/neurologicablog/index.php/scott-adams-on-science-
and-nutrition/)

~~~
melling
I'm not sure that matters. It's ok to eat cholesterol now, right? All these
"mistakes" give science a black eye. We've already got a Climate Change
trustworthyness problem and for some reason people don't trust vaccines,
mostly educated people. As a nation, we refused to fund both the Hubble and
the Supercollider, which would have been bigger than CERN.

It's probably time that we stopped making excuses and think of a better way to
explain the "science" to people.

~~~
SquareWheel
>It's ok to eat cholesterol now, right?

The position of "science" has been to eat a balanced meal and exercise for as
long as I can remember. You won't see a medical journal recommending fad
diets. Steve covers this fairly well in the article I linked.

But still, public outreach could be greatly improved. It's unfortunate that
many public doctors or educators on the subject are shills like Dr. Oz.

~~~
melling
You could start by providing the links to the science! Why should I trust what
you're saying? There's always someone on the Internet making claims. People
debate have raging debates and few people actually provide real data.

~~~
SquareWheel
Fair enough. :) Though in my case, showing where something "doesn't exist"
isn't the most possible. But there's plenty out there on recommending balanced
meals and exercise.

------
rpedroso
The author makes a few references to the idea of "scientific consensus", which
I find curious. It's a phrase that I tend to cast aside as politically
motivated. Politicians in the climate change debate like to point to
"scientific consensus" as a way of saying, "look, all these intelligent people
whose work we personally don't understand agree, so they must be correct."

But one tenant of scientific thought is that truth and factuality are not
measures of an individual's or society's belief, but rather, they are
discovered by experiments whose results can be replicated.

> _People distrust science when it conflicts with their valued beliefs, or
> when science suggests a solution or intervention that conflicts with their
> beliefs. People are happy to trust science when it does not conflict with
> their ideology or narrative._

I agree, but those same people generally rationalize those views to themselves
in the way Adams noted: by pointing at reasons to distrust science or
scientists. They get caught up in issues like "climategate", they assert that
results about medical science are distorted by financial pressures, etc.

In short, the rationalizations of individuals who reject scientific results
often point to the scientists behind the results, their interests and
motivations, instead of the results themselves. This isn't exclusively true,
but I think the tie in to the idea of "scientific consensus" is this:

Perhaps science would be better served by a decreased emphasis on the
individuals carrying out scientific research and increased emphasis on the
results themselves.

~~~
threeseed
> Perhaps science would be better served by a decreased emphasis on the
> individuals carrying out scientific research and increased emphasis on the
> results themselves.

No thanks.

One of the worst aspects of modern day science right now is that the media et
al seems to think it is okay to allow anyone to present counter arguments
regardless of their scientific background. This causes problems for the laymen
who has no ability to even comprehend let alone compare results from different
individuals. And it is laymen who ultimately determines what science gets
funded and what happens to the results of the science e.g. political action.

~~~
protonfish
The results of one study could mean anything and I agree it should not be
emphasized to the public.

However, the term "scientific consensus" makes truth sound like a popularity
contest and worse - a popularity contest by people who claim they are better
than you. This appeals to the authoritarian nature of people, not their
critical nature. It is basically telling the public they aren't allowed to
think. It's not only a jerk thing to do, it discourages scientific literacy
outside of scientific professionals.

Another problem with the "scientific consensus" is due to its political
influence and nebulous definition it is rife for abuse. If there is no
rigorous methodology to determine it in an accurate and replicable manner,
then it can be whatever someone says it is.

I agree that we need some sort of way of determining scientific validity by
taking into account many tests, theory and perpectives, but "Scientific
consensus" (whatever that is) is not it.

