Genetic Risk for Breast Cancer
- While most cases of breast cancer are driven by lifestyle factors, some cases are caused by genetic changes.
- The most well-known genes associated with breast cancer are the BRCA1 and BRCA2 genes.
- A new mutation that’s linked to an increased risk in breast cancer may have been discovered.
- According to a new study, scientists say a change within the ATRIP, which is required for proper cell division and cancer prevention, has been linked to an increased breast cancer risk in the Polish and the United Kingdom populations.
- While this is an important step in finding potentially unknown genetic links to breast cancer, more research is needed to know how widespread this mutation could be and how much it actually increases a person’s breast cancer risk.
Researchers may have discovered that a genetic mutation (change) within the ATR-interacting protein (ATRIP) gene could predispose women to develop breast cancer.Read More
Women carrying these genes have around a 70% chance of developing breast cancer in their lives. These odds famously led Angelina Jolie to choose to have her breasts removed (a procedure called a mastectomy) in 2013.
However, there are likely many other genes, most of which are not known, that may put women at risk. And scientists say their discovery of the ATRIP mutation’s association with breast cancer is an important step in fully understanding genetic breast cancer risk.
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WATCH: Understanding Breast Cancer Risk Factors
Breast cancer starts within the cells of the breast tissue. There are many kinds of breast cancers, such as ductal carcinoma in situ (DCIS; colloquially termed “pre-cancer”), invasive ductal carcinoma, and invasive lobular carcinoma, depending on which part of the breast turns cancerous.
Breast cancer is one of the most common cancers among women in the United States. An estimated 300,000 women will be diagnosed with the disease in 2023. Another 56,000 will be diagnosed with DCIS. The disease is expected to cause more than 43,000 deaths this year, per the American Cancer Society.
One in eight women will develop this cancer in her lifetime, which translates into a 13% lifetime risk.
Black women, as compared to white women, develop more aggressive forms (such as triple negative) of breast cancers earlier in their lives. They also face a higher rate of death from this cancer.
Genes and genetic changes can, however, greatly influence these numbers. Those with high-risk genes may be many, many more times susceptible to developing these cancers than those without.
Expert Breast Cancer Resources
Understanding ATR Interacting Protein (ATRIP)
Under normal circumstances, the ATRIP gene and its proteins play an invaluable role in ensuring that the DNA is replicated without errors (termed genomic stability) during cell division.
When DNA is damaged, a host of molecules and proteins recognize this damage and spring into action. These in turn recruit ATRIP proteins, initiating a series of reactions that ultimately stop the cell cycle. Altogether, this prevents faulty, erroneous DNA from being duplicated. If duplicated, such DNA can lead to a host of diseases, including the development of tumors and cancers.
What Does The Study Show About ATRIP?
The researchers were motivated to find yet unknown genes that may contribute to the development of hereditary breast cancers. They initially selected 818 women in Poland for the study.
The Polish population, especially the founder population, has less genetic variation than any large, mixed population. Therefore, they are more likely to carry risky genetic changes.
510 of these women were selected from a breast cancer registry. All had breast cancers in the setting of significant family histories. They had undergone genetic testing and were found to lack any of the known genetic mutations associated with increased cancer risk (such as BRCA1, and BRCA2). This meant that the genes responsible for their disease had not yet been identified.
An additional 308 cancer-free women without any significant family history of breast cancer were selected from a general registry for comparison purposes.
All subjects had their blood drawn for genetic analyses between 2007 and 2012. Genetic mutations that were known to increase the risk of cancer development were identified, of which the ATRIP mutation was the most common. This finding was subsequently tested in a larger group of Polish women. In this group, the mutation affected 0.3% of the women with breast cancer, while it affected only 0.1% of those without cancer.
The affected women also reported significant family histories of the disease. This was further confirmed in the British population with similar results.
“ATRIP is associated with a higher risk of breast cancer. Patients who have a mutation in the gene have over 200% higher risk of developing breast cancer than the average risk in the population. More importantly, the tumors of [such] patients show specific characteristics, which is indicative of response to PARP inhibitors, a special group of targeted therapy drugs,” says Dr. Mohammad R. Akbari, an assistant professor at the Dalla Lana School of Public Health, University of Toronto, and the principal investigator of the study.
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What Does This Mean?
The association of the ATRIP mutation with an increased breast cancer risk is an important finding. However, the scope of this finding should be assessed within the limitations of the above study.
The study focused on Polish women, who are known to have less genetic variation than more mixed populations. Although the study was validated within the U.K. as well, it is possible that this finding does not apply to the rest of the world.
In technical terms, it may lack generalizability. Thus, studies looking at diverse populations are needed for the ATRIP mutation’s association with breast cancer to become more robust.
Dr. Akbari explains, “This study is the first step in understanding the role of a new gene in hereditary breast cancer. However, more research is needed to explore the exact clinical implication of this new gene in the management of breast cancer patients. For this, we need to study the role of ATRIP in increasing breast cancer risk among other populations and study the response of the mutation carriers [to breast cancer medications, such as] PARP inhibitors.”
Additionally, the extent to which a particular genetic mutation increases the risk of breast cancer varies wildly. BRCA mutations, for example, make it 70% more likely for women to develop breast cancer. This is different from other mutations, which may only increase the risk by 20%.
This risk needs to be quantified for the ATRIP mutation for us to know just how much more at risk ATRIP carriers are for developing breast cancer.
Nonetheless, the identification of the ATRIP gene is a salient finding. It underscores the idea that there are many still unidentified genes that can increase the risk of breast cancer in the population.
“There are more breast cancer susceptibility genes that could be identified. Those new genes will explain the clustering of breast cancer in families with no identified mutation in previously known breast cancer genes,” emphasizes Dr. Akbari.
RELATED: Understanding Gene Mutations in Your Metastatic Breast Cancer Diagnosis Is Crucial to Your Treatment
Questions To Ask Your Doctor:
If you have been diagnosed with breast cancer in the past or have a family history of this cancer, you should discuss the genetic aspects of the disease with your physician:
- Do I have genetic mutations that increase my risk of developing breast cancer? Knowing your mutational status can help you manage this risk through diligent cancer screenings or regular physician visits.
- If I do have a genetic mutation, should my children be tested as well? Genetic mutations may make it more likely for your children to develop breast cancer.
- I was tested in the past for genetic mutations, but should I be tested again? New genes that contributed to an increased risk of breast cancer are being discovered day in, day out. Even if you have tested negative for mutations in the past, it may be worth it to get retested for some of the new genetic mutations.
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