genes & colon power

From: Damien Broderick (d.broderick@english.unimelb.edu.au)
Date: Sun Feb 11 2001 - 20:19:29 MST


>In short, it is not a colon cancer gene but a gene that affects our
>ability to respond to the environment. And that, says Venter, is what
>human nature is all about.

>http://www.guardian.co.uk/Archive/Article/0,4273,4134598,00.html

Here's a longer chunk, because I find the above cite slightly misleading:

===========
                        It is caused by an inherited
                               weakness in one gene that controls DNA
                               repair in other genes.

                               'But that gene is found in cells in every
                        part of
                               the body. However, it is only the colon where
                               we find all sorts of toxins and bacteria that
                               provides the harsh circumstances that final
                               causes that gene to finally break down and for
                               cancer to spread.'

                               In short, it is not a colon cancer gene but a
                               gene that affects our ability to respond to the
                               environment. And that, says Venter, is what
                               human nature is all about.
                   
======================

I assume Venter's actually saying this: it's a gene for a repair protein
that helps fix sequence damage, so that when it's trying to do its job in a
particularly damaging environment it too can get overwhelmed in turn, and
break. So of course it's not a gene *for* colon cancer. If anything, it's a
gene *against* colon (and all sorts of other) malignancies that sometimes
proves ineffective.

That gives me a chance to make a fool of myself with a thought about cancer
risk. It's such an obvious idea that it's either transparently wrong or
perfectly standard, but I don't think I've read it anywhere.

Ionizing radiation and some ferocious chemical mutagens aside, it strikes
me that maybe most cancers are likely to happen in tissues undergoing
repeated mitotic replacement. Plainly this accounts for lung, stomach
lining, bowel, blood, bone marrow, etc, although presumably not brain
cancers--unless they sneak in on the blood from elsewhere as secondaries.
If so, I wonder if some classically `harmful' behaviors might not be
carcinogenic per se, but simply conduce to rapid turnover of new tissue,
which stochastically increases the likelihood of getting the five or so
necessary mutations in the same cell to produce a malignancy.

If so, one might expect muscle builders to get more cancers in their
micro-torn tissues (but then there's also oxidative damage, of course), sex
maniacs to get testicular cancer, curry eaters to get stomach cancer
(assuming this ferocious stuff insults the lining and causes increased rate
of repair *without itself being mutagenic*), etc.

In short: many cancer-conducing hazards might not be primarily mutagenic
(as suntanning is, exposing tissues to ionizing radiation), but, by
increasing the turnover of cells, significantly multiply the chances of
accumulated oncogene and telomerase activation, suppression of repair
mechanisms, etc. If so, this might have implications for prevention and
treatment.

Damien Broderick



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