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Scientists track down prostate cancer risk to key ageing gene

A team of scientists from across the world – led by The Institute of Cancer Research, London – looked into genetic variation across a region of DNA associated with prostate cancer risk on chromosome 5.

The region contains a gene called TERT (telomerase reverse transcriptase), which is involved in safeguarding the length and ends of chromosomes – and therefore a key regulator of the ageing process.

The team took DNA samples from PRACTICAL, an international consortium giving scientists access to a huge bank of genetic samples. Researchers analysed 134 single nucleotide polymorphisms (SNPs) – pieces of DNA that vary between individuals – and did an additional computational analysis with 1,094 SNPs in over 40,000 men both with and without prostate cancer.

The findings revealed that four separate regions within the TERT gene are independently associated with prostate cancer risk. One of these regions containing the SNPs rs2242652 and rs7725218 was associated with activity of the TERT gene.

TERT is important in maintaining the correct length of the ends of chromosomes, which are called telomeres. Shortened telomeres are known to occur in many cancers and genetic variants in TERT are linked to other cancers, including lung, bladder, cervical, pancreatic and skin cancer. The variants identified in this study are linked with lower risk for prostate cancer, and show an association with increased levels of the protein product of the TERT gene. Elevated TERT activity – or expression – can provide better maintenance of the telomeres, potentially protecting against cancer.

Study researcher Dr Zsofia Kote-Jarai, Senior Staff Scientist said: “This work highlights the importance of looking into the regions identified by genome-wide association studies in more detail, so that we can pick out the relevant variants within these. Further studies are still needed to fully understand TERT’s involvement in prostate cancer risk, but these are very exciting results. We are rapidly adding to our ever expanding knowledge of prostate cancer risk variants, and ultimately we hope this information can be used to implement prostate cancer screening programmes.”

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