In recent years, nearly nine times more genetic tests have been carried out in Estonia than a decade ago. The sharp increase has been driven by advances in technology as well as Angelina Jolie, who publicly spoke about a gene mutation that raised her risk of breast cancer.

For a long time, Estonian doctors primarily screened patients for two of the most well-known gene mutations, including changes in the BRCA1 gene that posed a risk to Jolie. "At the same time, looking for only two common variants would have identified just 5.7 percent of patients affected by hereditary breast cancer," said the study's lead author, Mikk Tooming.

In neighboring Latvia and Lithuania, those two mutations account for the majority of all detected high-risk gene variants. In Estonia, however, the same mutations make up less than half of all identified cancer-risk-related changes. "We are not a population with just one or two founder mutations; rather, the risk variants originate from different sources and have developed over a long period of time," Tooming explained.

Still, researchers identified one harmful mutation in the BRCA2 gene that accounts for nearly one-fifth of all findings related to that gene in Estonia. This may indicate that the mutation originated in the region. In addition, analysis of the data revealed 25 entirely new disease-causing gene variants that have not previously been observed elsewhere.

Testing and awareness

Researchers conducted a retrospective analysis of data from more than 3,500 patients who underwent genetic testing between 2007 and 2023. The team identified a cancer-predisposing mutation in nearly one in five patients — about 19 percent of those tested. In addition to the well-known BRCA gene family, disease-causing changes were frequently found in other genes in Estonia, such as CHEK2 and PALB2. Both are tumor suppressor genes whose primary role is to prevent the proliferation of cells with damaged DNA.

A particularly strong hereditary link was observed in ovarian cancer where a disease-causing mutation was found in more than one-quarter of women. According to Mikk Tooming, such a high proportion points to a clear need to offer genetic testing to every ovarian cancer patient, regardless of family history. Researchers also recommend comprehensive genetic testing for all cancer patients under the age of 40. Genetic information can help doctors decide on the most appropriate surgical treatment or targeted therapies for each patient.

If a patient carries a hereditary gene variant, there is a 50 percent chance that the same mutation is present in their biological relatives. Tooming noted that people should consider testing in consultation with their family physician, particularly if there has been breast cancer in the family before the age of 50 or cases of bilateral breast cancer. Carriers of high-risk variants are advised to begin closer health monitoring from the age of 25. "Early testing and the implementation of preventive measures can significantly impact their lives," Tooming said.

Breast cancer is often mistakenly regarded as a disease affecting only women. However, the study highlighted the underestimated cancer risk among men. During the period studied, 97 men in Estonia were diagnosed with breast cancer, but only a quarter underwent genetic testing. Of the 24 men who were tested, one in three carried a hereditary cancer-related mutation.

In addition to increasing the risk of breast cancer in men, these genetic mutations also significantly raise the likelihood of prostate and pancreatic cancers. "Awareness among men is critical, as BRCA2 and other cancer risk genes also affect them," Tooming emphasized.

Need for a single database

On a more positive note, routine practice in the medical system has changed significantly in recent years. Nearly two-thirds of new genetic tests are now ordered by general specialists and oncologists, rather than only by medical geneticists. "This shows that genetic testing has become a natural part of standard oncological and gynecological care pathways," said Tooming. This helps speed up diagnosis and makes the patient's treatment journey smoother.

More comprehensive testing does have some drawbacks, however, as laboratories often detect gene variants whose impact on health is not yet clearly understood. In Estonia, patients are generally not informed about such findings, as they do not affect treatment decisions. Moreover, studies show that around 90 percent of these variants are later classified as benign. As a result, researchers say the benefits of broad-based testing clearly outweigh the potential confusion caused by uncertain findings.

In the coming years, more detailed genetic data will need to be integrated with national cancer registries. Currently, no registry in Estonia systematically collects molecular genetic data in a structured way, even though the country has the technical capability to do so. A unified system would allow doctors to assess patients' cancer risks in real time and proactively refer at-risk family members for testing. "Estonia's e-health solutions and biobank infrastructure are very strong; what is primarily needed is a clear national decision, common standards and system integration," Tooming added.

The study was published in the journal Scientific Reports.

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