Telomerase and Cancer Part 8

Yes it’s true I have written 8 different articles about cancer and telomerase since 2009 and I suppose I should prepare to write 8 more.

The most recent stir up in the field came from an internet news blitz entitled “Long Telomeres May Increase Cancer Risk” detailing the findings of an erudite Southern California lab based at the same University as Telomere Nobel Laureate Elizabeth Blackburn.

This group has major scientific star power and lots of science cred to back up what they say.

Naturally the “see we told you so” crowd picked up on this immediately and interpreted it as Telomerase causes cancer. The more they dislike me and what I do or the more I pissed them off in the past for not buying into what they are doing the more vociferous the email nasty grams.

One person even suggested “Your telomerase activators are giving people cancer and your book is full of deadly information!”

So after a week or so of this I did what it seems I have to do more and more often these days. Break my vow of silence and answer the questions directly all the while trying to remain nice, calm and objective.

So here is the background.

In this particular study the scientists were looking at a rare and deadly tumor known as glioma (there are several different forms of this brain cancer and none are good!).

They found an association with long telomeres and glioma and used a technique known as Genome Wide Association Study (GWAS) to establish a link to mutations “in the area of the telomerase gene” that “might “ account for the increases in Glioma they saw.

Using my least favorite way of determining telomere length QPCR they found said association in 3 different areas “related” to the telomerase gene.

More background: the telomerase gene and other “longevity genes” such as APO and glucose/insulin genes are located in areas that are hypermutatable for lack of a better term.  This means that more mutations than expected are found in these areas than many other areas of the genome.

The reason for this is unknown but please understand it is a well documented and rather widespread phenomenon that is not limited to the telomerase gene.

These mutations are called SNPs or single nucleotide polymorphisms because the result in one change in one molecule of DNA.

Please understand that SNPs are a favorite of scientists studying cancer and other diseases because if they can reproduce them in animal models then they can study the cancer that way. At the same time it is likely that most human cancers do not occur as SNPs but rather as epigenetically driven changes.

Even the most famous BRAC SNPs associated with breast cancer are estimated to account for 5% or less of human cancers. Put another way 95% of breast cancer is not due to these SNPs.

Also understand that SNPs are often inherited meaning the changes they cause in the genome are present from the time of conception until death. In terms of the SNPs that are associated with glioma they occur in the general population  between 50 and 70% of the time and are present in over half of the control group which is 4x larger than the cancer group. That control group did not get cancer.

Glioma is also associated with older age at the time of onset.  The older you are the more likely you are to get glioma. The control group that has no cancer and longer telomeres is likely to live considerably longer than an equal group with short telomeres.

Gliomas are also well known to use the ALT non telomerase method to lengthen their telomeres rather than increasing telomerase.

So here is my list of questions for the authors:

Why did you use QPCR the least accurate method of measuring MTL which misrepresents telomere dynamics and introduces a large potential for inaccuracy? My guess is once we get past all the other political stuff would be “Because that is what lots of other people are using!”

Next when does a SNP become considered normal?  If it’s present in over half of the population at large then how do we know it’s a mutation.

Finally did they factor in age at diagnosis as an independent risk factor since gliomas go up with age.

Now the truth is they did not need to look at all this stuff because they were not saying Telomerase Causes Cancer or Long Telomeres Cause Cancer ( again JAMA Dec 2010 showed exactly the opposite: short telomeres are associated with cancer!). They were saying mutations in the area of the telomerase gene are ASSOCIATED with one rare Cancer.

Big difference.

Especially when you consider that genetic mutations are forever and for life in many cases and cause elevations of gene products as well as dysfunctions of gene products that are not associated with short term telomerase activators.

In addition there is no data to suggest that using supplements like fish oil which appears to preserve telomere length, or TA-65 which may lengthen telomeres has ANY association with cancer of ANY kind in.

I applaud the scientific discoveries made by scientists and of course the use of GWAS is interesting in looking at SNPs. But I remind you the word associated does not mean cause. You could potentially find that eating pizza is associated with a higher death rate in motor vehicle accidents.

And we went through this last summer when a study cited a 2% change in Omega 3 levels as associated with a 73% increase in prostate cancer.

For most of us SNPs are the least of our worries. Shortening telomeres on the other hand is a 100% given. Read some of the other myths about telomeres and telomere supplementation here.




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