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Long Telomeres May Cause Lung Cancer

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Forest plots (left) and scatter plots (right) of associations between TL-associated SNPs and risk for lung adenocarcinoma (top) and squamous cell carcinoma (bottom). From: http://hmg.oxfordjournals.org/content/early/2015/07/24/hmg.ddv252.full

 

Scientists from the University of Chicago have found out that long telomeres are related to higher chances of lung cancer. The article, appeared in the journal Human Molecular Genetics, affirms that lung adenocarcinoma doubles in risk for every 1,000 base pair increase in telomere length (TL).

Telomeres are repetitive nucleotide sequences at the chromosome ends that protect them from being recognized as double strand breaks. The enzyme telomerase is able to elongate telomeres in stem cells, but becomes silenced when cells specialize. This causes telomeres to shorten with each cell division; cells die or enter into senescence after approximately 50 divisions. Short telomeres are thus considered undesirable, but the new finding goes against that notion. Previous reports on the subject already hinted at a TL-cancer relationship, but suffer from bias due to measuring TL after diagnosis. TL can vary due to cancer progression, and also to other factor such as age and lifestyle. To avoid that, Brandon Pierce´s team studied cancer relationship to nine TL-associated single nucleotide polimorphisms (SNP), changes in the genome that affect at least 1% of the population. Instead of measuring TL directly, they studied cancer incidence on patients with mutations previously known to cause long telomeres.

Mendelian randomization to estimate TL based on genetic factors

The researchers used inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long telomeres and cancer risk. After analyzing data from 51,725 cancer cases and 62,035 controls, they concluded that long telomeres were related to greater risk for lung cancer. Other cancer types analyzed (breast, colorectal, ovarian and prostate) did not show a correlation between the TL score and cancer risk. The authors speculate about longer TL allowing cells more time to accumulate mutations that lead to cancer.

source: genengnews

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