Tumor Markers

BRCA1 and  BRCA2

How will you define BRCA1 and BRCA2?

1. BRCA stands for the breast cancer gene (BReast CAncer gene).
2. The most important dominant genes are breast cancer susceptibility genes BRCA1 and BRCA2.
3. What is the location of the BRCA gene?
   1. The BRCA1 gene is present on chromosome 17q. It is a breast cancer type 1 susceptibility protein.
   2. The BRCA2 gene is present on chromosome 13q12-13.
4. BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins.
   1. These proteins help repair damaged DNA, ensuring the stability of a cell’s genetic material.
   2. Mutations in these genes can lead to a higher risk of developing certain cancers, particularly breast and ovarian cancer.

Tumor markers: Chromosome normal structure

How is the inheritance of the BRCA gene?

1. Breast cancer patients have an inherited predisposition to develop breast and ovarian cancer that is inherited as an autosomal dominant trait.
2. In these patients, two genetic loci have been identified and labeled as BRCA1 and BRCA2.
3. BRCA1 encodes 1863 amino acids protein that may act as a transcription factor.
4. Finding mutated BRCA1 and BRCAS2 genes in somatic cells helps to find the females who carry this mutated gene.
5. It is documented that ladies carrying one of these mutated genes are prone to developing breast or ovarian cancer.
6. BRCA1 gene mutation ladies have an 85% chance of developing breast cancer and a 45% chance of developing ovarian cancer by the age of 65 years.

What is the role of the BRCA gene as a tumor marker?

1. BRCA1 and BRCA2 are suppressor genes.
2. The BRCA gene indicates an increased susceptibility to the development of breast cancer.
3. In the case of a lady having breast cancer on one side, if she has a BRCA gene mutation-positive, then have a 65% chance of developing breast cancer on the other side, compared to the BRCA gene negative, where only 15% develop cancer.
4. The BRCA1 and BRCA2 mutations show 50% and 30%, respectively, breast cancer inheritance.
5. The BRCA1 mutation is estimated to have a 20 times greater risk by the age of 40 years compared to the general population.
   1. Lifetime risk is 60% to 85%.
   2. The White population is more prone to the BRCA1 mutation, which affects 3.3% of women.
   3. BRCA1 mutation is less common in the black population.
6. The ladies who show BRCA1 gene mutation are at greater risk of developing ovarian cancer,
   1. The ladies <2% develop ovarian cancer by the age of 70 years when there is no BRCA gene mutation.
   2. However, in women with BRCA gene mutation, 44% develop ovarian cancer by the same age of 70 years.
7. The BRCA gene mutation also increases susceptibility to ovarian cancer.

What is the mechanism of the BRCA gene?

1. These genes encode tumor suppressor proteins.
2. So any change or mutation in the gene may inhibit or retard its suppressor function leading to uncontrolled cell proliferation.
3. BRCA1 gene mutation also has increased the incidence of ovarian cancer.
4. Women with BRCA1 gene mutation develop:
   • Ovarian cancer in 44% of the ladies by the age of 85 years.
   •  Breast cancer in 85% of the ladies by the age of 85 years.
5. Women with BRCA 2 have a 20% chance of developing breast cancer.
   • Another source: Women by the age of 70 years, the chances for breast cancer are 45%.
6. 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. Of 100 women with positive BRCA 1/2, around 45 to 65 years of age will get breast cancer.

How will you screen the ladies with BRCA gene mutation?

1. Ladies need transvaginal ultrasounds at 6 to 12 months.
2. The CA-125 blood test should be done every 6 to 12 months.
3. Some BRCA 1/2 positive women never develop breast cancer.

How will you Summarize 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 that consists of 1863 amino acids.
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, an individual has an 85 % risk of developing breast cancer and 45 % of 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 was 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.