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Most types of cancer not due to “bad luck” [pdf]

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Re: Most types of cancer not due to “bad luck” [pdf]

#51
post #30

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…

Overall, it's not clear to me why this was published. The fifth paragraph explains why it was published: “Concluding that ‘bad luck’ is the major cause of cancer would be misleading and may detract from efforts to identify the causes of the disease and effectively prevent it.” It's fairly obvious that if a study tells people most cancers are caused by bad luck and not bad actions, there will be some subset of the pop…

> "if a study tells people most cancers are caused by bad luck and not bad actions"

Something to take into consideration. As far as I remember the original article talked about most "types" of cancers and it didn't refer to cancer cases. By volume, some cancers are common and very likely to have an environmental cause.

Re: Most types of cancer not due to “bad luck” [pdf]

#52
post #29

This shows a severe misunderstanding of statistics. The original paper (here: 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 div…

> That, in itself, is a fascinating scientific result There are plenty of problems with the original paper see http://www.sciencemag.org/content/347/6219/224.full http://arxiv.org/abs/1501.04605 http://www.iarc.fr/en/media-centre/pr/2015/pdfs/pr231_E.pdf

Thanks for these links.

The Science link is basically a retraction from the journalist who wrote the original summary article. She quotes the study authors making excuses about not having enough time to explain the subtleties under press deadlines. I've never read anything quite like it.

It seems everyone agrees that Figure 1 of the Vogelstein paper, showing the striking correlation between Log(cancer incidence) and Log(# stem cell divisions) was really a beautiful result. But then things fell apart with the further analysis and (especially) interpretation.

The Altenberg paper on Arxiv looks like exactly the sort of careful treatment that the original paper should have gotten in the review process. (MIT's Aaron Meyer raised some of these points in a blog post around the time of publication http://www.ameyer.me/science/2015/01/02/vogel.html )

Re: Most types of cancer not due to “bad luck” [pdf]

#53
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.

Re: Most types of cancer not due to “bad luck” [pdf]

#54
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 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.

Re: Most types of cancer not due to “bad luck” [pdf]

#56
post #17

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 'unluc…

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

Re: Most types of cancer not due to “bad luck” [pdf]

#57
post #25

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…

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 decision…

>> 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.

Re: Most types of cancer not due to “bad luck” [pdf]

#58

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 tr…

Your use of an imagined ignorant politician wielding the phrase 'scientific consensus' in the affirmative as a disagreeable act seems odd to me. It is generally the 'skeptic' ignorantly asserting 'there is no consensus' which brings focus to the concept in that debate:

"The skeptic attitude to consensus usually starts with “there is no consensus”. That’s wrong, and they usually retreat from it to “but consensus science is meaningless”, and/or “consensus has nothing to do with science”. The latter is largely true but irrelevant. The existence of the consensus doesn’t do a lot to determine what science is done; it doesn’t prevent contrary lines being explored. But the consensus view does come into the tricky interface between science and policy, and science and the media." [1]

> they assert that results about medical science are distorted by financial pressures, etc.

I'm not sure what you mean here? Much science conducted is so distorted by financial pressure that it isn't scientific. Consider how an entire area of research in the pharmaceutical industry should probably just be binned [2].

Considering this, it is more essential than ever in considering the individuals carrying out the research. As long as we have weak and corrupted regulatory systems there will be a continued distrust of any industry-sponsored research, and in many areas that's the research that dominates.

Until there's a global change in how research is funded and conducted there seems little hope of trusting that the output is very scientific.

[1] http://www.realclimate.org/index.php/archives/2004/12/just-w...

[2] http://www.badscience.net/books/bad-pharma/

Re: Most types of cancer not due to “bad luck” [pdf]

#59
post #38

This shows a severe misunderstanding of statistics. The original paper (here: 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 div…

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 big…

Yeah, we you look at total cancer burden and the associated epidemiology you can explain something like 90% of cancers from environmental sources (which includes things like obesity). Don't have a reference on me at the moment so feel free to disagree.

Re: Most types of cancer not due to “bad luck” [pdf]

#60
post #25

Earlier quoted context omitted.

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 decision…

>> 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.

> 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

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