Cancer as the telephone game

An interesting paper just out [ Science vol. 347 pp. 78 – 81 ’14 ] basically says that cancer is just bad luck due to copying errors of the 3.2 megaBase genome when cells divide. It’s a version of the telephone game in which a message is passed around a circle of people getting progressively garbled each time.

The evidence in support of the assertion is that the variation in cancer rates between tissues is strongly related to the number of divisions of the stem cells required to maintain that tissue. For instance the lifetime risk of being diagnosed with cancer is 7% for lung but .6% for brain (about this more later). Risk in the GI tract varies by a factor of 24 (.5% for the esophagus 4.8% for the colon) which is proportional to the number of stem cell divisions undergone during lifetime.

They estimate that at most 1/3 of the variation in risk among tissues is due to environmental factors or inherited predisposition. That’s certainly not to say that you should go ahead and smoke.

The idea makes a lot of sense. Even though the error rate in copying the parental genome to a child is an amazingly low 1/100,000,000 that still is 32 mutations per generation (more from the father than the mother and more from him the older he is, not so for the mother)– for details please see https://luysii.wordpress.com/2012/08/30/how-fast-is-your-biological-clock-ticking-ii-latest-results/.

There is even better evidence for this based on my clinical experience in neurology for 35+ years. The lifetime chance of a brain tumor is stated to be .6%. However in all these years I never saw a brain tumor made of neurons. They were all derived from glia (astrocytoma, glioblastoma) or the coverings of the brain (meningiomas). Why? Essentially neurons in the cerebral cortex (not the deeper parts of the brain) don’t divide. [ Cell vol. 153 pp. 1183 – 1185, 1219 – 1227 ’13, Science vol. 340 pp. 1180 – 1181 ’13 (Editorial) ] Even the parts that do divide add a trivial amount of neurons to the brain (700 neurons a day). Even if you live 100 years — that’s only 100 * 365 * 700 == 26 million neurons, a trivial amount compared to the 100 billion neurons you are estimated to have (this number grows each time I read about it).

You might be interested in how we can make statements like this about new neuron formation in the brain. It’s very clever — Carbon-14 accumulated in the atmosphere between the mid 50s and early 60s as a byproduct of above ground testing of nuclear weapons. Such testing was banned by treaty in 1963 and carbon-14 levels in the atmosphere declined in the following decades to previous low background levels. Carbon-14 is used in archeologic dating because its halflife is 5730 years.

Using postmortem tissue samples of individuals born before and after the nuclear bomb tests, the integration of carbon-14 into genomic DNA was measured. This would have occurred during the cell’s last division cycle. One can calculate the birth dates of different cell types collected from various tissues including brain. The approach is accurate to within a few years. The 5730 year half life of 14-C means that whatever is in human DNA hasn’t had a chance to decay (by much) in 50 years. The amount of carbon-14 in cellular DNA therefore reflects the amount of carbon-14 in the atmosphere when the cells underwent their last division. The amount of carbon-14 in the atmosphere was determined by measuring it in the annual growth rings of pine trees in Sweden — a surrogate for atmospheric carbon-14 levels in the past 60 years. The birthdate of cells is determined as the year the C-14 in them matches those of the pine trees.

Advertisements
Post a comment or leave a trackback: Trackback URL.

Comments

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: