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New discovery explains how a common gene variant may increase cancer risks


Roughly 15 percent of the population carries a gene variant that may increase the risk of developing cancer. The cause of this increased risk has been unknown until now. But now a research team at Stockholm University in Sweden can explain why.

“The variant makes the cell motor sputter and mutate, so cancer can arise,” says Associate Professor Thomas Helleday, who leads the research team at the Department of Genetics, Microbiology, and Toxicology, Stockholm University.

Even though it is easy to identify the some 15 percent of the population who have the harmful gene, which is called XRCC3 T241M, it is not meaningful to examine them since there are also other unknown factors that influence if this variant increases risk of cancer.

“On the other hand, we can possibly make use of the faulty variant to custom design new treatments in the future. And even if this doesn’t happen, it’s nevertheless important to understand the mechanisms that make certain individuals more susceptible to cancer than others,” he says.

Normally our genes have to be divided into two perfectly identical copies when a cell divides. The unfortunate variant causes a defect in the division of the genetic material (mitosis), which means that a daughter cell may get too few or too many genes. If a daughter cell does not receive a gene that prevents cancer, a so-called tumour suppressor gene, then a cancer can grow. One defence mechanism against cancer is for a cell that gets faulty genes to commit suicide (apoptosis). The defect caused by the unfortunate variant when it divides the genes is so tiny that the suicide mechanism does not detect the fault, which allows the cell to continue its growth into a cancer.

“The variant causes just a tiny defect that cannot be detected by the defence mechanisms against cancer. Just as in life, minute mistakes can lead to fatal consequences if they are not discovered,” says Thomas Helleday.

The main financiers of this research are the Swedish Pain Relief Foundation and the Swedish Cancer Society, and the findings are published in the April issue of the journal Human Molecular Genetics.

Maria Erlandsson | alfa
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