The RAD51D gene provides instructions for creating a specific protein within the human body. This gene belongs to a larger family involved in maintaining genetic material stability. Understanding its function helps clarify how our cells normally operate.
The Role of the RAD51D Protein
The protein produced from the RAD51D gene plays a role in homologous recombination, a DNA repair process. This process is active when double-strand breaks occur in DNA. The RAD51D protein acts like a cellular “mechanic” that identifies and meticulously mends these breaks. It works alongside other proteins to accurately repair damaged DNA using a healthy copy as a template. This repair mechanism is important for preserving genome integrity, preventing errors that disrupt cell function.
RAD51D Gene Mutations and Cancer Risk
When a RAD51D gene mutation occurs, the protein may not function correctly. This impairs the cell’s ability to perform homologous recombination, leading to unrepaired DNA damage and genetic instability. Cells with these errors can acquire additional mutations, potentially leading to uncontrolled growth and cancer.
Women with a pathogenic RAD51D mutation have an increased lifetime risk for certain cancers, particularly ovarian and breast cancer. The lifetime risk for ovarian, fallopian tube, or primary peritoneal cancer is estimated to be 10% to 20%, compared to 1.3% in the general population. For breast cancer, the lifetime risk is about 20%, versus 12.5% in the general population. Studies also indicate that breast cancers associated with RAD51D mutations are more likely to be triple-negative, a type that lacks certain hormone receptors and can be more aggressive.
Genetic Testing and Family Implications
Genetic testing offers a way to determine if an individual carries a RAD51D gene mutation. This testing is recommended for people with a personal or strong family history of ovarian or breast cancer, particularly if these cancers occurred at younger ages or in multiple relatives. The test involves providing a blood or saliva sample, analyzed for specific changes in the RAD51D gene.
A RAD51D mutation is hereditary, inherited in an autosomal dominant pattern. This means if one parent carries the mutation, each child has a 50% chance of inheriting it, regardless of sex. Identifying a mutation in one family member has implications for other blood relatives, who may also be at increased risk and could benefit from genetic counseling and testing.
Medical Management for Mutation Carriers
For individuals carrying a RAD51D mutation, medical management strategies are recommended to reduce cancer risk or detect cancer at an earlier stage. These strategies involve increased surveillance and risk-reducing procedures, guided by professional organizations like the National Comprehensive Cancer Network (NCCN).
Ovarian Cancer Risk Management
Clinicians may discuss risk-reducing salpingo-oophorectomy (removal of the ovaries and fallopian tubes), often considered between ages 45-50, or earlier based on family history of early-onset ovarian cancer. While ovarian cancer surveillance with transvaginal ultrasound and CA-125 blood tests may be considered, their benefit in early detection for high-risk individuals is currently uncertain.
Breast Cancer Risk Management
For breast cancer risk, women with a RAD51D mutation are advised to begin regular breast cancer screening at a younger age, such as annual mammograms starting around age 40, or earlier depending on family history. Clinical breast exams every 6-12 months, starting around age 25, are also part of recommended surveillance. Discussions about yearly breast MRI with and without contrast are also included. These proactive measures are tailored in consultation with genetic counselors and medical teams, considering an individual’s specific circumstances and family history.
Targeted Cancer Therapies
Knowing about a RAD51D gene mutation can directly influence treatment decisions if cancer develops. This is particularly relevant for targeted therapies, designed to attack cancer cells while minimizing harm to healthy cells.
Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of targeted drugs approved for treating certain cancers in individuals with RAD51D mutations. These drugs exploit the weakness in DNA repair within cancer cells that harbor a RAD51D mutation. By inhibiting PARP, these drugs prevent cancer cells from repairing minor DNA damage, leading to irreparable damage and cancer cell death. This approach offers a promising treatment option for patients with RAD51D-associated cancers, including advanced ovarian and metastatic prostate cancer.