Breasts at risk: researchers decipher hundreds of variants of breast cancer gene

22. 09. 2023

Breast cancer is the most common type of cancer in women. It can affect about one tenth of the population. Researchers have now succeeded in describing the significance of hundreds of inherited mutations in the CHEK2 gene that cause this cancer. The results of an extensive interdisciplinary collaboration led by Libor Macourek from the Institute of Molecular Genetics of the CAS and Zdeněk Kleibel from the First Faculty of Medicine, Charles University have been published in the Clinical Cancer Research journal.

The CHEK2 gene has long been in the crosshairs of clinical geneticists. It is the third most frequently affected gene associated with intermediate risk of breast cancer in the Czech Republic. Some of its inherited mutations expose carriers to a nearly 30 percent lifetime risk of the disease.

However, the presence of many other variants of the CHEK2 gene has so far prevented reliable quantification of the risk for most women who carry this mutation. “In our laboratory at the Institute of Molecular Genetics of the Czech Academy of Sciences, we have developed a unique experimental procedure that has allowed us to evaluate hundreds of previously unclear variants of the CHEK2 gene,” Lenka Stolařová explains.


Risk variants
Thanks to the new methodology, CHEK2 gene variants captured in cancer patients from around the world can be analysed in a model system in cell cultures. “Thanks to this, we were able to distinguish between pathogenic CHEK2 variants contributing to breast cancer and functionally insignificant variants that do not affect this risk,” Libor Macůrek adds.

“Thanks to the joint efforts of the national CZECANCA consortium and the international ENIGMA consortium, we have been able to screen more than 80,000 patients from twelve countries and demonstrate that the newly described risk variants of the CHEK2 gene are present in approximately 0.5% of all women with breast cancer,” explains Petra Kleiblová from the General University Hospital in Prague who, together with Zdeněk Kleibl, leads the CHEK2gether project of the ENIGMA consortium.

Certain cancers are caused by hereditary traits. Thanks to the development of genetic testing in recent years, the methodology has become increasingly successful in finding patients at increased risk of developing breast cancer and enrolling them in prevention or early detection programmes during which the disease can be treated efficiently.

The most well-known examples of hereditary breast cancer are mutations in the BRCA1 and BRCA2 genes, which cause the disease in 60–80% of carriers. However, in addition to mutations in these genes, there are a number of other, less well-studied inherited variants that increase the risk of breast cancer. The main benefit of the study in question will be to improve the quality of care for women with CHEK2 gene mutations not only in the Czech Republic, but on a worldwide scale.

Breast cancer is currently one of the most serious epidemiological problems in the Czech Republic. Over 7,200 new cases are diagnosed every year, which is more than 133 patients per 100,000 Czech women. Approximately 1,600 patients die of breast cancer every year, which corresponds to more than 30 deaths from breast cancer per 100,000 women.

The study published in Clinical Cancer Research can be found here.

The press release issued by the Institute of Molecular Genetics of the CAS can be found here.

A story on the subject also appeared in the CAS magazine A / Věda a výzkum as “Insatiable cancer cells” (in Czech), published online in English as Researching the way cancer cells communicate brings hope for new treatment.

Prepared by: Markéta Wernerová, External Relations Division, CAO of the CAS, drawing on the CAS press release; statistics sourced from
Photo: Shutterstock; Institute of Molecular Genetics of the CAS

Licence Creative Commons The text is released for use under the Creative Commons license.

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