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Survival, a function of how much telomerase is produced?
From my archives
http://www.cancerwise.org/June_2005/print.cfm?id=532D2B2B-3832-43A2-BFD0AD197E4AAF24&method=Disp...
June 2005 MD Anderson:

Gene Variant Predicts Brain Tumor Survival
Enzyme Related to Chromosome Length Holds the Key

A large study of patients with glioblastoma multiforme, a deadly form of brain cancer, has found that a genetic variation appears to double the survival rate.

The study of 301 patients, presented recently by M. D. Anderson scientists at the annual meeting of the American Association for Cancer Research, establishes the strongest link to date between genetic variation and clinical outcome. Researchers found that the 36 patients (about 11%) who had the “SS” variant of the hTERT gene survived an average of 25 months, compared to about 14 months for those who had either the “SL” or “LL” genotypes.

hTERT produces human telomerase, an enzyme that helps regulate the length of telomeres, the structures that cap the end of chromosomes. In cancer, it is believed that telomerase is activated and intervenes to keep telomeres from shortening, allowing for unlimited division of cancer cells.

Positive results pave way for future research

Lead investigator Melissa Bondy, Ph.D., a professor in M. D. Anderson’s Department of Epidemiology, says the findings are exciting because they suggest new treatment directions for a brain tumor that is common, but offers little hope of survival for patients.

“It is a real advance because we have never seen any genotype that can stratify glioblastoma multiforme patients into different treatment outcome groups like this,” Bondy says. “Now we need to verify the finding, study the mechanism, and see if there is a way that these results can be used either as a biomarker or to individualize treatment.”

For example, if the SS variant of hTERT is confirmed to have better response to chemotherapy and radiation treatment, then it is possible that these therapies will extend survival for patients with glioblastoma multiforme, she says.

hTERT genetic variation is mysterious and promising

The research group looked at genetic variation of hTERT because an abnormal production of the gene contributes to unregulated cell growth, and production of the gene has been evaluated as one of the most common tumor markers in most primary tumors, says the study’s first author, Luo Wang, M.D., Ph.D., a research scientist in the Department of Epidemiology.

Exactly why patients with the SS variant of hTERT showed better survival remains unknown. But some forms of hTERT may be less destructive to cancer cells than others because they may be produced at a lower level, Wang says.

The association between the SS variant genotype and improved outcome held up, even when differences in age, sex and the extent of surgery, chemotherapy and radiation were taken into account. “We have looked at a lot of different genes associated with cancer, such as DNA repair genes and p53, but this is the first time we have found a genotype that has such a large effect on clinical outcome,” Wang says.