Characteristics of the test : (includes 1 gene)

BRCA1 (OMIM# 113705)

Basic characteristics of the clinical phenotype:

Family members have been found to suffer from the same diseases such as diabetes, allergies, heart disease, cancer and more. Carcinomas are multifactorial diseases, for the development of which both genetic and environmental factors have a role. Age, body weight, lifestyle, hormonal and dietary factors, ionizing radiation and environmental pollutants are only some of the predisposing environmental factors for the development of oncological diseases. Of the genetic factors predisposing to the occurrence of breast and ovarian cancer, mutations in the BRCA1 and BRCA2 genes play a major role. The two genes are responsible for the synthesis of proteins that support the normal functioning of cells by participating in important processes, including the repair of DNA damage, the control of protein synthesis, cell division and cell death.

Indications  for Referral/Clinical Significance:

● Early onset of the disease (under 45 years of age);

• Several relatives affected by breast and/or ovarian cancer on one side of the family (maternal or paternal);

• Bilateral breast cancer (both breasts are affected);
  Cancer of the breast and ovaries/fallopian tubes/peritoneum in one family member;

• Men with breast cancer;
  Triple negative breast cancer;
  A variant with a pathogenic effect, found in the family.

• Several cases of breast/ovarian cancer on one side of the family (maternal or paternal) in combination with cases of one or more of the following oncological diseases: fallopian tube, peritoneal, prostate, thyroid, endometrial, pancreatic cancer; diffuse carcinoma of the stomach; leukemia; lymphoma; brain tumors;
  
  

Interpretation of results:

● Mutations in the BRCA1/ BRCA2 genes are associated with an increased risk for breast, ovarian and bilateral breast cancer;

● Recent studies show that for BRCA1 mutation carriers, the average risk of developing these cancers by age of 70 is 65% (50% - 80%) for breast cancer, 32% (24% - 40%) for ovarian cancer and an average of 27% for the development of a tumor in the other breast (4). For carriers of BRCA2 mutations, the risks are respectively 55% (40% - 70%) for breast cancer, 14.5% (11% - 18%) for ovarian cancer and an average of 12% for the development of a tumor in the other breast;

● In men, mutations in these genes are associated with an increased lifetime risk for breast cancer (1-10%) and prostate cancer (39%); 1-7% risk for pancreatic cancer and a small risk for the development of certain other types of cancer;

● In healthy women carrying BRCA1/ BRCA2 mutations, it is recommended that preventive examinations of the breasts and ovaries with ultrasound diagnostics begin at an early age (under or at the age of 25) and be performed every six months by specialist mammologists and gynecologists;

● Once a year, a breast examination with nuclear magnetic resonance is recommended, which has a better resolution than routine mammographic examination;

● In men, carriers of BRCA1/BRCA2 mutations, prophylactic examinations, including breast and prostate imaging, are recommended every 12 months after the age of 35.

 

Method: MLPA (Multiplex Ligation-Dependent Probe Amplification)

MLPA analysis is a semi-quantitative method for determining copy number variations of DNA. The methodology is used to detect intragenic or whole-gene deletions or duplications. The analysis for searching for large BRCA1 gene deletions and duplication is performed using the kit SALSA MLPA probemix P002 BRCA1, developed by  MRC-Holland (Amsterdam, Holland).

Sensitivity of the method: 90%;

What does the test involve:

● DNA isolation and sample storage;

● MLPA analysis to detect deletions/duplications that affect the studied regions of the BRCA1 gene;

● Forming a written result from the genetic test;

● Diagnostic interpretation of results and genetic counseling.


Biological material: Venous blood or DNA isolated from venous blood.

For more information, please read carefully the "Biological Material Requirements and Transport Information".