Same data, two opposite conclusions? – unless…

Ed Park, MD cancer, dr ed park, News, Telomerase activation, Telomere erosion Leave a Comment

When data from the Copehnhagen City Heart Study was published in 2013, they concluded that shorter telomeres in leukocytes was not associated with increased cancer after adjusting for age but that it WAS associated with reduced survival from cancer

In 2015, the same data looked at certain gene tendencies that promote telomere shortening and concluded that cancer survival was IMPROVED when shortening was enhanced in the telomeres.

Contradiction? Not so fast.

The static snapshot of telomere shortening in 2013 might have been associated with more aggressive tumors, weaker immunity, and poorer health.

So damaged telomeres carried a poor prognosis at the time of diagnosis in the 2013 analysis but that group was not subdivided into people with and without telomere maintenance mutations.

The 2015, this seemingly contradictory study using the same data looked at telomere maintenance mutations. In it, subjects’ ability to maintain already damaged telomeres, including those of cancer stem cells, resulted in IMPROVED survival, possibly because the poor maintenance allowed for cancer stem cells’ descendents to die out by replicative senescence and mutation more easily..

This may seem counter-intuitive but imagine a bank hostage situation: If you send in guns (as with telomerase activation) the hostages (i.e. the good guy immune cells) might overwhelm the bad guys.

If you poison the air system as with telomerase maintenance deficits, the good guys might again overwhelm the bad guys as is hoped when we use chemotherapy.

But if the bad guys and the good guys are both really bad at keeping themselves alive from these telomere maintenance problems, the bad guys might self-destruct faster, again explaining why survival was better with telomere maintenance problems in 2015 even though the snapshot analysis of all shorter telomeres in 2013 might have suggested otherwise.

What’s good for the goose is good for the gander. In other words, stem cell viability for healthy cells via telomere maintenance is beneficial for stem cells we want and those we don’t: cancer stem cells.  In the big picture, there has been a mountain of evidence showing that telomere shortening increases risk of cancer so whatever you can do to prevent this initial creation of cancer stem cells should be helpful.

The truth is complicated but with patience and wisdom, perhaps a more complete picture can be envisioned without throwing out either study.

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