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Bad luck, bad journalism and cancer rates

188 pointsby auton1over 10 years ago

10 comments

waldrewsover 10 years ago
Oy vey. Statistician&#x2F;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 &quot;biological luck,&quot; 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.<p>Let&#x27;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.<p>It&#x27;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)<p>I don&#x27;t like the use of the word &quot;luck&quot; 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.
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Gatskyover 10 years ago
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.<p>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.<p>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&#x27;s hardly a revelation that a larger more cellular organ is more likely to get cancer.<p>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&#x27;t even true, but anyway). This contradicts the whole hypothesis, but they still include it in there.<p>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.<p>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.<p>I don&#x27;t think this warrants much attention in the end. This can join the 100,000 other unverified (or unverifiable correlations) in the cancer literature.
therealdrag0over 10 years ago
I want to reiterate the articles recommendation of the book &quot;Bad Science&quot; by Ben Goldacre [0]. I learned a lot from it and found it enjoyable--and it&#x27;s available in Audiobook form.<p>[0] <a href="http://smile.amazon.com/Bad-Science-Quacks-Pharma-Flacks/dp/0865479186/" rel="nofollow">http:&#x2F;&#x2F;smile.amazon.com&#x2F;Bad-Science-Quacks-Pharma-Flacks&#x2F;dp&#x2F;...</a>
toufkaover 10 years ago
Here&#x27;s the deal - we know it&#x27;s &#x27;chance&#x27; (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 &#x27;taken care of&#x27; by the cell which caries that DNA - either by literally repairing the DNA, silencing that DNA&#x27;s function, killing itself, or asking other cells to help kill it.<p>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&#x27;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.<p>Cells that deviate from what they&#x27;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 &#x27;go, no-go&#x27; 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 (&#x27;cancer&#x27;). 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&#x27;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).<p>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.<p>So again, we quite clearly know of a handful of genes which do most of the master regulation of a cell&#x27;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.
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vasilipupkinover 10 years ago
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?
leg100over 10 years ago
What&#x27;s the difference between bad luck and &quot;we just don&#x27;t know&quot;?
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ekianjoover 10 years ago
Wait, is this an article from the Guardian making fun of their own article on the same study earlier on ? See <a href="http://www.theguardian.com/society/2015/jan/01/two-thirds-cancer-cases-caused-bad-luck-lifestyle-genes" rel="nofollow">http:&#x2F;&#x2F;www.theguardian.com&#x2F;society&#x2F;2015&#x2F;jan&#x2F;01&#x2F;two-thirds-ca...</a> ? If that&#x27;s the case, that&#x27;s a novel way of doing journalism: publish crap first, then sell more paper by doing a critique of your crap.
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dangover 10 years ago
Also <a href="https://news.ycombinator.com/item?id=8827666" rel="nofollow">https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=8827666</a>.
termostaattiover 10 years ago
Naturally the way one lives has an impact whether potentially he&#x2F;she will get cancer. Smoking, drinking, eating certain types of food (manufactured wrong) etc. all have direct relation on cancer. It&#x27;s never just <i>luck</i> who happens to get these horrible diseases.
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MisterMashableover 10 years ago
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&#x27;m a believer in vaccines so don&#x27;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.