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Fourteen new breast cancer risk genes discovered

German Cancer Research Center News Jun 23, 2018

The family risk of women whose immediate family members suffer from breast cancer is about twice as high as that of the general population. A large number of genetic markers associated with the increased risk are already known. These markers are usually identified by so-called genome-wide association studies. Researchers are testing millions of tiny genome variants that differ from each other only in a single DNA component (SNPs "single nucleotide polymorphisms") for association with the breast cancer risk.

"We are particularly interested in SNPs associated with gene expression in breast tissue. We assume that they will help us to identify genes that contribute to breast cancer development through altered activity," said Jenny Chang Claude from the German Cancer Research Center (DKFZ). The scientist is one of the authors of a recently published study, along with numerous other colleagues from the DKFZ. The aim of the international project was to identify unknown genes that might be involved in the development of breast cancer. To this end, the researchers first identified SNPs that are associated with altered expression of individual genes. These SNPs were then examined for an association with the breast cancer risk. Under the leadership of Wei Zheng of the Vanderbilt University Medical Center, more than 160 research groups worldwide participated in the study.

Genetic analyses of 229,000 women were included in the study, more than half of whom had breast cancer. Studies of such dimensions are necessary in order to be able to make statistically reliable statements on the individual SNPs.

In the end, the scientists identified 48 genes whose altered expression is significantly associated with an increased breast cancer risk. Fourteen of them were not yet known to be associated with breast cancer. The scientists specifically switched off 13 of the 48 genes that had a particularly strong risk association in various breast cancer cell lines. In 11 cases, this has led to changes in cell growth and the ability to form colonies—both are considered important mechanisms in the development of cancer.

The scientists now want to characterize all genes identified in the study more precisely. They hope that this will lead to a more precise understanding of the tumor biology of breast cancer. It may also be possible to detect previously unknown cancer-relevant signaling pathways that could be blocked with targeted active substances.

The study was published in Nature Genetics.

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