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The internet is full of cures for cancer and the medical literature (and many newspaper headlines) are full of claims about which specific lifestyle factors make cancer more likely. Some cancers are known to be strongly related to lifestyle (smoking is bad, in case anyone didn't know that already).

A recent headline in Gizmodo (and other sources) claims that most cancer mutations are random and unrelated to lifestyle factors (and , therefore, unavoidable):

In a study that’s bound to attract considerable controversy, a pair of researchers are claiming that between 60 and 66 per cent of all cancer-causing mutations are the result of random DNA copying errors, making them essentially unavoidable.

Is this claim true and the science behind it reasonable and correctly reported?

  • Nice question, I also meant to ask it – Sklivvz Mar 24 '17 at 13:25
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    Do cancer-causing mutations necessarily cause cancer? – gerrit Mar 24 '17 at 14:31
  • @Sklivvz i must be doing something right if i get to ask questions before you! – matt_black Mar 24 '17 at 15:05
  • @gerrit By definition, surely. Though not all mutations cause cancer, i assume that assume the way we know that some do (and are therefore called cancer-causing) is that they cause cancer. – matt_black Mar 24 '17 at 15:07
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    Important caveat: X% of cancer-causing mutations are unavoidable is not the same as X% of cancers are unavoidable, because there's more to causing cancer than just the mutations - there's also the cancer micro-environment and beating the body's defences. For example, tobacco smoke doesn't just cause potentially cancer-causing mutations, it also reduces the effectiveness of NISCH, the "cancer suppression gene". Even if 100% of mutations were unavoidable, some cancers would still be attributable to lifestyle and environmental factors like this. – user568458 Mar 24 '17 at 15:26
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The actual research paper Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention Science 24 Mar 2017: Vol. 355, Issue 6331, pp. 1330-1334 says:

It is now widely accepted that cancer is the result of the gradual accumulation of driver gene mutations that successively increase cell proliferation (1–3). But what causes these mutations? The role of environmental factors (E) in cancer development has long been evident from epidemiological studies, and this has fundamental implications for primary prevention. The role of heredity (H) has been conclusively demonstrated from both twin studies (4) and the identification of the genes responsible for cancer predisposition syndromes (3, 5). We recently hypothesized that a third source—mutations due to the random mistakes made during normal DNA replication (R)—can explain why cancers occur much more commonly in some tissues than others (6).

...

This hypothesis has generated much scientific and public debate and confusion, in part because our analysis was confined to explaining the relative risk of cancer among tissues rather than the contribution of each of the three potential sources of mutations (E, H, and R) to any single cancer type or cancer case. Determination of the contributions of E, H, and R to a cancer type or cancer case is challenging. In some patients, the contribution of H or R factors might be high enough to cause all the mutations required for that patient’s cancer, whereas in others, some of the mutations could be due to H, some to R, and the remainder to E. Here we perform a critical evaluation of the hypothesis that R mutations play a major role in cancer. Our evaluation is predicated on the expectation that the number of endogenous mutations (R) resulting from stem cell divisions in a tissue, unlike those caused by environmental exposures, would be similarly distributed at a given age across human populations. Though the number of stem cell divisions may vary with genetic constitution (e.g., taller individuals may have more stem cells), these divisions are programmed into our species’ developmental patterns. In contrast, deleterious environmental and inherited factors, either of which can directly increase the mutation rate or the number of stem cell divisions, vary widely among individuals and across populations.

...

The median proportion of driver gene mutations attributable to E was 23% among all cancer types. The estimate varied considerably: It was greater than 60% in cancers such as those of the lung, esophagus, and skin and 15% or less in cancers such as those of the prostate, brain, and breast. When these data are normalized for the incidence of each of these 32 cancer types in the population, we calculate that 29% of the mutations in cancers occurring in the United Kingdom were attributable to E, 5% of the mutations were attributable to H, and 66% were attributable to R. Cancer Research UK estimates that 42% of these cancer cases are preventable. Given the mathematical relationship between cancer etiology and cancer preventability (see supplementary materials), the proportion of mutations caused by environmental factors is always less than the proportion of cancers preventable by avoidance of these factors. Thus, our estimate that a maximum of 29% of the mutations in these cancers are due to E is compatible with the estimate that 42% of these cancers are preventable by avoiding known risk factors.

...

A cancer in which 50% of the mutations are due to R can still be preventable. The reason for this is that it generally requires more than one mutation to develop the disease. A cancer that required two mutations is still preventable if one of the mutations was due to R and the other due to an avoidable environmental factor.

Our results are fully consistent with epidemiological evidence on the fraction of cancers in developed countries that are potentially preventable through improvements in environment and lifestyle. Cancer Research UK estimates that 42% of cancer cases are preventable

So, in summary, in the UK, they find:

Mutations due to Environment (E): 29%

Mutations due to Heredity (H): 5%

Mutations due to normal DNA replication (R): 66%

So once you have been conceived, only 29% of cancer causing mutations are avoidable, but considering that more than one mutation may be required to cause a particular cancer, the authors find this consistent with 42% of cancer cases being preventable.

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