Woman examining her breasts for cancer
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Several new genes strongly associated with breast cancer have been identified in a large-scale, international, collaborative study. The research used genetic data from 26,000 women with breast cancer and 217,000 women without the disease, including women from eight countries in Europe and Asia.

These new genes, although rare, could eventually be included in tests to identify women at increased risk of breast cancer.

“Improving genetic counselling for high-risk women will promote shared decision-making regarding risk reduction strategies, screening and determination of treatment options,” says Jacques Simard of Université Laval, a co-senior author of the study.

“Although most of the variants identified in these new genes are rare, the risks can be significant for women who carry them. For example, alterations in one of the new genes, MAP3K1, appear to give rise to a particularly high risk of breast cancer,” he adds.

The work was published last week in Nature Genetics. The lead author was Naomi Wilcox of the University of Cambridge, and it was jointly supervised by Simard and Professor Douglas Easton at the University of Cambridge.

“We knew already of 10 or so genes associated with breast cancer, with BRCA1, BRCA2, PALB2, ATM and CHEK2 being the most important,” Easton tells Inside Precision Medicine.

He adds that, “We also know that there are common, mainly non-coding gene alterations that are associated with breast cancer. However, these are not sufficient to account for all the hereditary component of breast cancer. So, we were confident that there were other genetic effects to find.”

He points out that most previous studies of breast cancer risk genes have concentrated on a more limited subset of genes, particularly those involved in DNA repair.

This study found evidence for at least four new breast cancer risk genes and evidence for others. The discovery of these novel genes will not only guide diagnosis, it also provides crucial information on the biological mechanisms underlying cancer development, opening the way to identifying new treatments.

Although previous genes, such as BRCA1 and BRCA2, have been identified through tracking in families, Easton noted that this approach only works for relatively common high-risk genes, so direct sequencing is really the only viable approach to find more. This team, he said, wass able to make use of very large studies from colleagues in the Breast Cancer Association Consortium, as well as data from the very large UK Biobank Cohort.

“To our knowledge, this is the largest study of its kind. It was made possible through the use of data from multiple collaborators in many countries, as well as publicly available data from the UK Biobank,” says Easton.

Before this information can be used in a clinical setting, scientists need to validate the results in further datasets.

“We need additional data to determine more precisely the risks of cancer associated with variants in these genes, to study the characteristics of the tumors, and to understand how these genetic effects combine with other lifestyle factors affecting breast cancer risks,” says Easton.

The research team is currently pursuing a large-scale international effort designed for this purpose. The next steps include conducting a further large validation study, to evaluate the new genes in non-European populations, and to conduct functional experiments in some genes to determine which variants in the genes are likely to be risk associated and why.

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