Cancer incidence and “bad luck”

This one had even the presenters of the BBC’s weekly statistics fest “More or Less” scratching their heads.

The confusing abstract here: says

‘These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells.’

Tomasetti C, Vogelstein B. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. Published online January 2 2015.

Note the key phrase here “among tissues”, not “between individuals”. The study aimed to confirm the old and widely accepted theory that cancer is an inherent design flaw in all multicellullar organisms and that some level of cancer was an inevitable result of the rapid cell division that is essential for the maintenance of certain tissues (skin for example). However they did not look at cancer rates in individuals, only in different types of tissues.

Data was not available for all the possible tissue types. “Moreover, Dr Tomasetti and Dr Vogelstein were unable to include two of the most common cancers (breast and prostate) in their analysis, because the relevant stem-cell data are not available for these. What their study does explain is the long-known but curious phenomenon that apparently similar parts of the body suffer different rates of cancer. ”

This left the researchers with a relatively small set of data for tissues, from which it is hard to draw definite conclusions. “the estimate was quite variable, with 95% confidence intervals ranging from 39% to 81%. So only 4 out of 10 cancers may be a result of bad luck, or, alternatively, as many as 8 out of 10.”…/Are-most-cancers-down-to-bad-luck.aspx.

Also, according to coverage elsewhere (I’ve not seen the full paper), there were some exceptions to the general conclusion. “In some cancers [ie cancer types], environmental factors and inherited genetic factors did compound [ie significantly affect] the risk.”…/Are-most-cancers-down-to-bad-luck.aspx.

In particular, “The remaining third of cancer types, which are affected by [environmental] lifestyle factors, viruses or a heightened family [ie genetic] risk, include some of the most common:

Basal cell carcinoma – a type of skin cancer made more common by too much UV exposure
Lung cancer – strongly linked to smoking
Colon cancer – increased by poor diet and family risk genes”

One study alone is not enough to draw a definitive conclusion from. “Separate research by Cancer Research UK shows more than four in 10 of the total number of cancers were down to lifestyle.”

Also, even if the original study had been correctly interpreted and accurately reported, it would still be wise to avoid those risks that individuals can control, particularly smoking.

The original study was widely reported in the media as “the majority of cancer is due to bad luck”. However that was criticised in the Guardian. That article suggests that the only conclusion you can draw is that the majority of the variation in relative cancer risk between tissues is due to random genetic malfunctions during cell division. The key word here is “relative”, the implication is that the study says nothing about the actual absolute numeric risk of cancer in a particular tissue (not even in an individual person). The baseline risk across all tissues (if all cell division could be abolished) could take any absolute numeric value, from zero up to 100%.

The authors of the original paper seem to have retreated from their original headline-grabbing claim, now that their future careers have been boosted by the publicity. “We have not showed that two-thirds of cancer cases are about bad luck. Cancer is in general a combination of bad luck, bad environment and bad inherited genes.”
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X-Men: First Class – fails Genetics 101

Maybe Xavier was drunk, or concentrating on chatting up girls, but he really should have known that the majority of genetic variation in a typical population of individuals comes not from mutation creating new genes (as he seemed to imply), but from the recombination (shuffling) of the existing genes.

Mutations are typically immediately lethal (even before an embryo reaches maturity), or at best crippling. For example, a fruitfly with legs instead of antennae on its head does not have the benefit of any super-power!

The shuffling of the existing pack of genes is much less disruptive to an organism and much more likely to result in a more successful individual. Thus most evolution is driven by such recombination, not by mutation.