BRCA1 & BRCA2 Impact More Cancer Types Than Previously Understood, Large Study Shows
If you've heard of BRCA gene mutations, you probably associate them with breast and ovarian cancer. This connection has been well-established for years, and it's shaped how doctors approach genetic testing and cancer screening for millions of people.
But new research suggests the BRCA story is bigger than we thought. A study published in ESMO Open found that BRCA1 and BRCA2 mutations are also linked to four additional cancer types. And the findings could have significant implications for how we think about genetic risk and personalized medicine.
A primer on BRCA mutations
Before diving into the new findings, it helps to understand what this mutation is and who carries it. BRCA1 and BRCA2 gene mutations can be passed down from either parent, and they increase cancer risk in both women and men.
In the general U.S. population, BRCA mutations are relatively rare — about 1 in every 400 to 800 people carry it. However, this proportion varies significantly by ethnic group. The mutation is more common among Ashkenazi Jews (people of Eastern European Jewish descent). In this population, about 1 in 40 carry a BRCA1 or BRCA2 mutation.
This difference shows up in cancer diagnoses too. Ashkenazi men and women are much more likely to develop breast cancer in their lifetime.
What the research found
Researchers conducted a case-control analysis of 3,489 patients with nine less common cancer types and over 38,000 controls without cancer, all from BioBank Japan. They were looking for associations between BRCA1 and BRCA2 pathogenic variants and cancers beyond the ones we already know about.
The results revealed four significant associations that had not been previously documented:
- BRCA1 mutations increased thyroid cancer risk by more than 5 times. (An association also existed between BRCA2 and thyroid cancer, but it was not statistically significant.)
- BRCA2 mutations increased bladder cancer risk by nearly 5 times.
- BRCA2 mutations increased head and neck cancer risk by nearly 4 times
- BRCA2 mutations increased skin cancer risk by more than 6 times
The study also calculated lifetime cumulative risk for carriers. For BRCA1 carriers, the cumulative risk of thyroid cancer up to age 85 was 10.1%. For BRCA2 carriers, the cumulative risk was 9.0% for skin cancer, 8.3% for head and neck cancer, and 12.8% for bladder cancer in women (compared to 5.6% in men).
The significance for women
The impact of BRCA2 mutations on bladder cancer risk was dramatically different between sexes.
Women with BRCA2 mutations had a 23-fold increased risk of bladder cancer, compared to just over 2-fold in men. The researchers noted that female bladder cancer patients with BRCA2 mutations had no past medical history of breast or ovarian cancer, suggesting this isn't simply a case of secondary cancers in people already diagnosed with BRCA-related malignancies.
Why such a dramatic difference? The researchers suggest that cystitis, which causes an inflammation in the bladder and is more common in women, may play a role. Inflammation can promote DNA damage, and individuals with BRCA2 mutations have reduced DNA repair capacity.
What to do if you carry a BRCA mutation
If you already know you carry a BRCA1 or BRCA2 mutation, this research suggests it may be worth having a broader conversation with your doctor about screening and surveillance. While clinical guidelines haven't yet been updated to reflect these findings, being informed gives you more agency in your own health decisions.
Some of these cancers have been reported to respond to PARP inhibitors, a class of drugs already used to treat BRCA-related breast and ovarian cancers. Identifying associations between BRCA mutations and these less common cancers could strengthen the rationale for clinical trials and expand treatment for people who currently have few options.
Here are some practical steps to consider if you are a carrier of this gene:
- Talk to your doctor or genetic counselor about what these findings might mean for your personal risk profile
- Stay informed as research evolves. Studies like this one are laying the groundwork for more comprehensive screening recommendations.
- Ask about emerging treatment options if you're facing a diagnosis, particularly whether PARP inhibitors might be relevant for your situation.
- Don't panic. Having a BRCA mutation doesn't mean you'll definitely develop these cancers. It just means staying proactive about your health is especially important.
If you haven't been tested for the BRCA mutations, but suspect you might have it due to Ashkenazi Jewish heritage and/or a family history of these cancers, it may be worth setting up an appointment with a genetic counselor. They will help determine if you qualify for testing, and will walk you through all the following steps.
The takeaway
For the millions of people who carry these mutations or have family with these mutations, this news might be alarming. But remember: information is power. And this study is enabling you to take all possible precautions to mitigate any future cancer risks.
It's also reminder that personalized medicine is still evolving, and that staying informed and engaged with your healthcare team is one of the most empowering and important things you can do for your long-term health.