[sf-lug] Cancer is mostly due to bad luck...

[Rick Moen]

Bobbie Sellers wrote:

> Of course cancer is bad luck but prevention has its place
> because it can make your luck a lot worse if you do things
> that might promote cancer.
> https://www.scientificamerican.com/article/most-cancer-cases-arise-from-bad-luck/

This is a follow-on to a 2015 paper by the same authors (Tomasetti and
Vogelstein) that suffered badly misleading headlines in the popular
press such as _Time_ magazine's 'Most cancer is beyond your control'
_The Guardian's_ 'two-thirds of adult cancers largely "down to bad luck"
rather than genes' and BBC's 'Most cancer types "just bad luck"', which 
poorly reflected what the authors said.  Also, the paper itself had
quite a few methodological flaws.

This new 2017 paper is an attempt to clarify, but is proving to also
have problems both in its contents and in third-party coverage that once
again gets it wrong.

_The Atlantic_ covers all of this.
https://www.theatlantic.com/science/archive/2017/03/no-cancer-isnt-mostly-bad-luck/521049/

About the 'bad luck' characteristion:

   'Such headlines were disastrously wrong. For a start, Tomasetti and
   Vogelstein looked at the differences between _body parts_, not _people_.
   Their data explained why tumors are more likely to strike the bowel
   than the brain, but not _this_ bowel versus _that_ one.  As oncologist 
   Vinay Prasad tweeted 
   (https://twitter.com/VinayPrasad82/status/845064997508046848): 
   “[Their] paper does not explain to cancer patients why they got 
   cancer.  [It] explains why cancer doctors get more colon cancer
   consults than sarcoma consults.”

In the 2017 paper;

   [...] the team have clearly emphasized that these numbers 
   _don’t tell us what proportion of cancers are preventable_. 
   It can take several mutations to trigger a case of cancer, so 
   even if _one_ of those was due to an avoidable environmental factor, 
   that cancer could still have been prevented.  That’s why, as the 
   team stressed, their finding that 66 percent of mutations are 
   randomly acquired is totally consistent with other estimates that 
   42 percent of cancer cases are preventable.  Mutations don’t equate 
   to cases.

   Try telling that to the _Daily Mail_, _Sun_, and _Forbes_, which all 
   ran headlines ascribing the majority of cancer _cases_ to bad luck. 
   The British charity Cancer Research UK made the same error in a post
   describing the team’s work.  _Stat_ avoided that pitfall, but when
   _Scientific American_ reprinted their story, they bowdlerized the 
   headline into “Most Cancer Cases Arise from ‘Bad Luck.’

That's the _Scientific American_ article you cited, FYI.

In addition to the distortive promotion (again) by third-party
publications including (sadly) _Scientific American_, Tomasetti and
Vogelstein once again are, according to critics in the profession,
making some critical scientific errors, such as, in the view of
statistical geneticist Song Wu at Stony Brook University, overestimating
the proportion of R-mutations, those that arise during normal DNA
replication without outside triggers (and are thus R=random and
unpreventable).  Tomasetti and Vogelstein took the total number of DNA
mutations in their study, subtracted those caused by known oncogenes and
by known environmental risk factors, and concluded the rest are caused
by R-mutations.  But this would be true only if we knew _all_ oncogenes
and _all_ environmental risk factors.  So, they are badly overestimating
the incidence of R-mutations.

As an example, consider studies of cervical cancer before the role of
HPV virus as a cause was known.  Tomasetti and Vogelstein's method would
have lead to a conclusion that all cervical cancer mutations were
R-mutations, and that the disease wasn’t preventable.  But it is.  It's
virus-caused, and we now have a vaccine for it.

That's the unknown unknown problem (to borrow that Rumsfeldism).
Tomasetti and Vogelstein also fail to account for known unknowns. 
Again, quoting what Song Wu and other critics said as quoted in _The
Atlantic_:

   [The study failed to recognise] sources of environmental risk that
   are clearly present, but still undefined.  Consider prostate cancer. 
   The team calculated that a whopping 95 percent of prostate cancer 
   mutations are R-mutations, which would make the disease almost entirely
   unpreventable.  "That just doesn’t make sense,” says Yaniv Erlich, a 
   geneticist at Columbia University and the New York Genome Center.
   There are substantial differences in prostate cancer rates between
   different countries.  If the disease was mainly caused by random
   replication errors, rates should be the same everywhere you look—and
   they clearly aren’t.  Indeed, immigrants who move from countries with 
   low rates to those with high ones tend to pick up the higher risk of 
   their new homes.  The environment clearly matters for prostate cancer; 
   it’s that we don’t yet know _which_ factors are important.

And about those 'unprevantable' R-mutations:

   And even if a particular cancer is entirely caused by R-mutations, it
   might not be unpreventable, as sites like Smithsonian [link] and_NPR 
   [link] have reported.  Aspirin, that most familiar of drugs, might 
   help to reduce the risk of colorectal cancer, as well as other types 
   like esophageal and pancreatic.  Some scientists are looking to drugs 
   like aspirin as ways of halting the evolution of cancer, by reducing 
   the rate at which mutations occur in the first place.  And as cancer 
   scientists move beyond their traditional focus on mutated genes, it 
   may become possible to prevent tumors by targeting surrounding cells, 
   reducing inflammation, or stimulating the immune system.

I strongly recommend the piece in _The Atlantic_.