The PALB2 gene is recognized for its role in hereditary cancer risk, particularly concerning breast cancer. Like BRCA1 and BRCA2, alterations in PALB2 can significantly increase an individual’s susceptibility to certain cancers. Understanding its implications is important for families navigating hereditary cancer predispositions, guiding discussions about risk assessment, genetic testing, and management strategies.
The PALB2 Gene’s Normal Role
The PALB2 gene, which stands for Partner And Localizer of BRCA2, plays a role in maintaining the stability of our genetic material. It codes for a protein that works in close cooperation with the BRCA2 protein. Together, these proteins are involved in a process called homologous recombination, a method cells use to repair damaged DNA.
When DNA is damaged, the PALB2 protein helps to recruit and stabilize BRCA2 at the sites of DNA breaks. This collaboration ensures that DNA damage is accurately fixed, preventing errors that could lead to uncontrolled cell growth. The PALB2 gene is considered a tumor suppressor gene, meaning its normal function helps to prevent the formation of tumors by ensuring proper DNA repair.
PALB2 Mutations and Cancer Risk
Mutations in the PALB2 gene impair its DNA repair function. When the PALB2 protein does not work properly, DNA damage accumulates, increasing the likelihood of cells becoming abnormal and potentially cancerous. These mutations are typically inherited.
For women, a PALB2 mutation significantly increases the lifetime risk of developing breast cancer, with estimates reaching up to 63% by age 80, compared to approximately 12% in the general population. Men with a PALB2 alteration also face an increased risk of breast cancer, with about 1% developing the disease. Beyond breast cancer, PALB2 mutations are associated with a slightly elevated risk of other cancers, including ovarian and pancreatic cancer.
Identifying PALB2 Mutations
Genetic testing is the primary method for identifying PALB2 mutations. It is generally recommended for individuals with a personal or family history suggestive of a hereditary cancer syndrome. Indicators include a strong family history of breast or ovarian cancer, or a breast cancer diagnosis before age 45.
The testing process involves providing a sample, such as blood or saliva, from which DNA is extracted and analyzed for changes in the PALB2 gene. Results can indicate a positive finding (a pathogenic mutation is present), a negative finding (no known pathogenic mutation is detected), or a variant of uncertain significance (VUS), meaning a change was found but its clinical impact is not yet fully understood. Genetic counseling is an important part of this process, both before and after testing, to help individuals understand the results and make informed decisions.
Managing Cancer Risk with a PALB2 Mutation
Individuals identified with a PALB2 mutation can take proactive steps to manage their elevated cancer risk. Increased surveillance for breast cancer is a common recommendation for women, often starting around 30 years of age. This involves more frequent screenings, such as annual mammograms and breast magnetic resonance imaging (MRI), along with regular clinical breast exams.
Risk-reducing surgeries are another consideration. For breast cancer, a prophylactic mastectomy (surgical removal of one or both breasts) can significantly reduce risk. For ovarian cancer, a prophylactic oophorectomy (removal of the ovaries and fallopian tubes) may be discussed. Certain medications, known as chemoprevention, can also reduce breast cancer risk. Lifestyle factors, such as maintaining a healthy weight, limiting alcohol, and regular physical activity, may also play a role in overall cancer risk reduction.
Treatment Approaches for PALB2-Related Cancers
When cancer develops in an individual with a PALB2 mutation, its presence can influence treatment decisions. Because PALB2 is involved in DNA repair, cancers arising from a faulty PALB2 gene may respond differently to certain therapies. For instance, targeted therapies like PARP inhibitors (poly ADP-ribose polymerase inhibitors) can be effective. These drugs exploit existing DNA repair deficiencies in cancer cells, leading to their death.
Standard cancer treatments, including chemotherapy, radiation therapy, and surgery, remain components of care for PALB2-associated cancers. The specific approach and sequencing of these treatments may be tailored based on genetic information. Understanding the PALB2 mutation allows oncologists to consider therapies that leverage the tumor’s unique biological vulnerabilities, aiming for personalized and effective outcomes.