Inherited Cancer Risk Higher Than Previously Thought: Nearly One in Five Relatives of Cancer Patients Carries High-Risk Mutations

In 2013, actress Angelina Jolie drew global attention to hereditary cancer after revealing that she carried a harmful BRCA1 gene variant. Because of her significantly increased risk of breast cancer, she chose to undergo a preventive double mastectomy.

Her decision sparked widespread interest in genetic testing. However, not everyone who carries a cancer-associated mutation requires preventive surgery. In many cases, identifying inherited risk early allows for enhanced surveillance, helping detect cancer at an earlier, more treatable stage.

A new study published in Frontiers in Genetics suggests that hereditary cancer risk is considerably more common than previously believed.

Researchers from the Institute of Clinical Medicine at the University of Tartu analyzed genetic testing results from 3,472 Estonian individuals who underwent testing between 2007 and 2023. All participants were healthy relatives of patients with breast or ovarian cancer in whom physicians suspected a hereditary cancer syndrome.

The findings were striking: 19.7% of participants—nearly one in five—were found to carry pathogenic genetic variants that substantially increase the risk of developing cancer. Among men, the prevalence was even higher, with 34% carrying disease-associated mutations.

The researchers noted that many carriers of these genetic variants were identified well before the age at which national cancer screening programs typically begin. The average participant was 41 years old, about a decade younger than the usual starting age for screening in Estonia, and nearly 79% of participants were even younger than that.

The highest likelihood of detecting a pathogenic mutation was observed in individuals under the age of 30. However, harmful variants were also identified in participants older than 71—an age at which routine screening programs have generally ended. These findings suggest that inherited cancer risk deserves attention throughout much of a person's lifetime.

Overall, the researchers identified 23 different pathogenic variants, although nearly 59% of all detected mutations were found in the well-known BRCA1 and BRCA2 genes, which are strongly associated with an increased risk of breast, ovarian, and several other cancers.

Family history also proved highly informative. Among participants who already had a relative with a known pathogenic mutation, the same genetic variant was identified in 41.8% of cases. Even among those whose families had no previously documented pathogenic mutations, 8% were found to carry high-risk genetic variants.

The authors also emphasized that men remain underrepresented in hereditary cancer testing programs, despite the fact that carrying mutations—particularly in BRCA2—is associated with an increased risk of prostate cancer and several other malignancies.