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Breast cancer is the most prevalent cancerous disease among women worldwide. Environmental factors and lifestyle, along with the influence of hormones, trigger cancer. However, genetics also significantly contributes to an individual's increased risk of developing breast cancer. Understanding these genes can aid in early detection and preventive strategies. This blog explores specific genes that may increase the risk of breast cancer, contextualizes the statistics within global and Indian events, and aims to provide a deeper understanding of the issue.
Key genes that affect breast cancer risk
Several genetic mutations, most of which are hereditary, influence breast cancer. Here's a little closer look at the most important genes involved in the breast cancer risk profile:
The BRCA1 and BRCA2 genes
The two most significant genes known to associate with an increased risk of breast cancer are the BRCA1, short for Breast Cancer 1, and the BRCA2, or Breast Cancer 2. These genes provide for the repair of damaged DNA; as long as they function properly, cancer cannot develop. Mutations within these same genes result in a failure to correctly repair DNA, thereby greatly increasing the potential for the development of cancerous growths.
BRCA1 mutation: Woman possessing this mutation will have a 55-72% lifetime risk of developing breast cancer, based on National Cancer Institute findings.
BRCA2 mutation: This type of mutation provides a 45–69% lifetime risk of developing breast cancer.
Both of these mutations also enhance the risk for ovarian cancer. Therefore, routine genetic testing for BRCA mutations allows women to prepare for prevention through enhanced surveillance or preventive surgery.
TP53 Gene
The TP53 gene expresses a protein called p53. The protein acts as a tumor suppressor that helps limit the growth of abnormal cells. Many cancers, including breast cancers, have mutations in this gene. A female who inherits a mutation in the TP53 gene is at increased risk for developing breast cancer—at a younger age.
Mutations in TP53 are associated with several genetic syndromes, including Li-Fraumeni syndrome, predisposing to a variety of cancers, including leukemia, breast cancer, and sarcomas. We recommend testing for TP53 mutations in extremely close families with multiple cancer types.
PALB2 Gene
The PALB2 gene interacts with BRCA2 in DNA repair. Similar to mutations in the BRCA1 and BRCA2 genes, the PALB2 gene also increases the risk of breast cancer. Current research finds that women with a mutation in the PALB2 gene have a lifetime risk of developing breast cancer of 33-58%.
Though PALB2 mutations are less common than BRCA mutations, they are no less an important cause of hereditary breast cancer. Patients with a family history of breast cancer often recommend genetic testing for PALB2.
CHEK2 Gene
The CHEK2 gene produces a protein that assists in the process of DNA repair. A mutation in this gene can impair the body's ability to monitor abnormal cell growth, placing it at risk of developing breast cancer.
Estimates place the lifetime risk of breast cancer in the range of 20–40% for women carrying a CHEK2 mutation. Apart from this, mutations of the CHEK2 gene may also lead to an enhanced risk for other cancers, including colon and prostate cancer. Families with a history of breast cancer are increasingly conducting genetic testing for CHEK2 mutations.
ATM Gene
The ATM gene generates a protein that assists the cell in repairing DNA damage resulting from radiation or other environmental exposures. Mutations in this gene may contribute to an increased risk of developing breast cancer, albeit at a lower lifetime risk than for BRCA mutations.
The ATM gene mutation is associated with a 20–30% increase in the risk of breast cancer in women. We recommend genetic screening for the above mutation for individuals with a family or personal history of breast cancer, regardless of the number of family members.
PTEN Gene
Another tumor suppressor gene is PTEN, whose mutation predisposes an individual to the development of breast cancer. The PTEN mutation causes Cowden syndrome, a rare genetic disorder that increases the risk for several cancers, including thyroid and uterine cancers, in addition to breast cancer.
Women with Cowden syndrome have up to a 50% lifetime risk of developing breast cancer. Women affected by this syndrome should seek regular cancer screening as well as take other preventive measures against cancer.
CDH1 Gene
The CDH1 gene promotes the interaction of cells with each other and also promotes cell-to-cell communication. Researchers have demonstrated that lobular breast cancer, a subtype of breast cancer, is responsible for alterations within this gene. Women with a CDH1 mutation have a strongly increased risk of developing breast cancer. Researchers estimate the lifetime cumulative risk for lobular breast cancer among women with a CDH1 mutation to be as high as 39-52%.
This gene also predisposes to gastric cancer, and carriers of a CDH1 mutation are closely followed for both forms of cancer.
The importance of genetic testing.
Genetic testing can help a woman and her doctor understand her risk for developing breast cancer. If there is a family history of breast or ovarian cancer, then a genetic counselor would be a suitable place to start the conversation. Testing can determine whether mutations in BRCA1, BRCA2, and other relevant genes have occurred, which influences decisions surrounding surveillance and prevention.
Since genes play a major role in the risk of breast cancer, genetic testing could become a means for early detection and prevention. We can direct women with a family history of breast cancer or at high risk to receive genetic counseling and testing for mutations in the BRCA1, BRCA2, PALB2, TP53, and other genes that may predispose an individual to cancer.
Individuals can work with their healthcare professionals to design an individualized plan to monitor and prevent cancer if they find an inherited mutation. This could include more frequent mammograms or breast MRIs or even preventive surgeries, such as mastectomy or oophorectomy.
Conclusion
Both genetic and environmental factors contribute to the multigenic nature of breast cancer. Such explanations regarding the roles of genes like BRCA1, BRCA2, etc. can motivate an individual toward beneficial decision-making for their lives. Breast cancer statistics are grim, not only in the world arena but also in India, and advance knowledge about genetic testing, early detection, and personalized treatments gives ample hope to patients who are at risk. We advise persons with a family history of breast cancer to visit a genetic counselor to discuss the possibility of testing as a preventive measure, as this could significantly reduce their risk of contracting the disease or catching it at an early stage.
If you have concerns about your breast cancer risk, it's best to consult with a breast cancer specialist who can assess your individual risk factors
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