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BRCA1 / BRCA2, Genetic Testing

BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are genes that produce proteins that help repair damaged DNA. Everyone has two copies of each of these genes, one copy inherited from each parent.

People who inherit harmful variants in one of these genes have increased risks of several cancers, most notably breast and ovarian cancer, but also several additional types of cancer. People who have inherited a harmful variant in BRCA1 and BRCA2 also tend to develop cancer at younger ages than people who do not have such a variant.

A harmful variant in BRCA1 or BRCA2 can be inherited from either parent. Each child of a parent who carries any mutation in one of these genes has a 50% chance of inheriting the mutation. Inherited mutations are present from birth in all cells in the body.

Even if someone has inherited a harmful variant in BRCA1 or BRCA2 from one parent, they would have inherited a normal copy of that gene from the other parent (that’s because in most cases, embryos with a harmful variant from each parent cannot develop). But the normal copy can be lost or changed in some cells in the body during that person’s lifetime. Such a change is called a somatic alteration. Cells that don’t have any functioning BRCA1 or BRCA2 proteins can grow out of control and become cancer.

According to the WHO, there are over 1.5 million annual cases of breast cancer worldwide. In Greece, about 6 thousand new cases are recorded annually. It is estimated that 1 in 8 women (worldwide) will develop breast cancer at some point in their lives. The high mortality of breast cancer is the most important problem. There is almost 13% mortality in the first year of diagnosis and overall, it is the leading cause of cancer death in women. The effectiveness of treatment is higher in the early stages of the disease. Early diagnosis of the disease is a key prerequisite for a substantial reduction in breast cancer deaths.

Breast cancer is an extremely heterogeneous disease. It is known that 5-10% of breast and ovarian cancers are inherited and can be attributed to gene mutations in the BRCA1 and BRCA2 genes. Both genes increase the risk of breast cancer by 80-85% in women as they approach the age of 80. The BRCA1 and BRCA2 genes encode nuclear proteins found in all cells. These proteins are involved in regulating DNA repair and maintaining genome integrity. Studies in families with BRCA1 and BRCA2 mutations show that mutations are inherited in an autosomal dominant manner.

BRCA1 mutations - which are associated with breast cancer - have been shown to have a higher incidence of malignancy, a higher incidence of malignancies with negative estrogen and progesterone receptors, a higher incidence of cancer with lymph node infiltration, and significant heterogeneity in treatment outcome.

The BRCA1 and BRCA2 genes are not completely specific for breast cancer. The abnormal genotypes BRCA1 and BRCA2 increase the risk of developing ovarian cancer, stomach cancer, colon cancer, pancreatic cancer, bladder cancer, head and neck tumors, endometrial cancer, and breast cancer.

Indications for genetic testing of BRCA1 / BRCA2 are:

  • Breast cancer at a young age (<50 years)
  • Aggravated family history (two or more blood relatives with breast and/or ovarian cancer)
  • Breast cancer in both breasts
  • Breast cancer and ovarian cancer
  • Triple-negative breast cancer (ER-, PR-, HER2 / neu tumors)
  • Breast cancer in men with a personal and family history

See also:

BRCA1 / BRCA2, Full Gene Analysis with NGS

BRCA1 / BRCA2, Full Gene Analysis with NGS and MLPA

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