Tumor Marker:- Part 6 – BRCA1, BRCA2, Significance in Breast Cancer

BRCA1 and  BRCA2 facts:

1. BRCA stands for the breast cancer gene.
2. The most important of the dominant genes are breast cancer susceptibility genes BRCA1 and BRCA2.
   • BRCA1 gene is present on chromosome 17q.
     • BRCA2 gene is present on chromosome 13q12-13.
   • BRCA1 and BRCA 2 are suppressor genes.
   • BRCA gene indicates an increased susceptibility for the development of breast cancer.
   • In the case of a lady having breast cancer on one side, if she has BRCA gene mutation-positive then have 65% chances of developing breast cancer on the other side, in comparison to the BRCA gene negative where only 15% develop cancer.
3. The BRCA1 and BRCA2 mutations show 50% and 30% respectively breast cancer inheritance.
4. The BRCA1 mutation is estimated to have a 20 times greater risk by the age of 40 years compared to the general population.
   • Lifetime risk is 60 to 85%.
   • The White population is more prone when having the BRCA1 mutation and is seen in 3.3% of ladies.
   • BRCA1 mutation is less common in the black population.
5. The ladies who show BRCA1 gene mutation are at greater risk to develop ovarian cancer,
   1. The ladies <2% develop ovarian cancer by the age of 70 years.
      1. But women with BRCA gene mutation, 44% develop ovarian cancer by the same age of 70 years.
6. BRCA gene also gives increased susceptibility to ovarian cancer.

Mechanism: These genes encode tumor suppressor protein.

1. So any change or mutation in the gene may inhibit or retard its suppressor function leading to uncontrolled cell proliferation.
2. BRCA1 gene mutation also has increased the incidence of ovarian cancer.
3. Women with BRCA1 gene mutation develop:
   • ovarian cancer in 44% of the ladies by the age of 85 years.
   •  Breast cancer is 85% of the ladies by the age of 85 years.
4. Women with BRCA 2 have 20% chances to develop breast cancer.
   • Another source: The women by the age of 70 years the chances for the breast cancers are 45%.
5. Another source:
   1. By the age of 70 years:
      1. In 100 women without BRCA 1/2, around 7 women will get breast cancer.
      2. In 100 women with positive BRCA 1/2, around 45 to 65 will get breast cancer.

Screening of the ladies with BRCA gene mutation:

1. Ladies need transvaginal ultrasound  6 to 12 months.
2. The CA-125 blood test should be done every 6 to 12 months.

• In some BRCA 1/2 positive women, they never develop breast cancer.

Summary of BRCA antigen:

BRCA1

1. This is called the breast cancer gene.
2. This gene is located on chromosome 17q.
3. BRCA1 encodes for a protein which consists of 1863 amino acid.
4. Breast cancer with BRCA1 has an exceptionally high proliferation rate.
5. Breast cancer with BRCA1 has overexpression of p53.
6. Mutation of the BRCA1 gene individual has an 85 % risk of developing breast cancer and 45 % for ovarian cancer by the age of 85 years.

BRCA2

1. This is called the breast cancer gene.
2. BRCA2 is located on chromosome 13q12-13.
3. BRCA2 also has a higher proliferation than BRCA negative cases.
4. Mutation of BRCA1 and BRCA2 found in individuals with a family history of breast cancer.
5. Mutation in one of these genes carrying women may develop breast cancer or ovarian cancer.
   

   BRCA1 and BRCA 2

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