Tumor Marker:- Part 6 – BRCA1, BRCA2, Significance in Breast Cancer
BRCA1 and BRCA2 facts:
- BRCA stands for the breast cancer gene.
- 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.
- BRCA1 gene is present on chromosome 17q.
- The BRCA1 and BRCA2 mutations show 50% and 30% respectively breast cancer inheritance.
- 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.
- The ladies who show BRCA1 gene mutation are at greater risk to develop ovarian cancer,
- The ladies <2% develop ovarian cancer by the age of 70 years.
- But women with BRCA gene mutation, 44% develop ovarian cancer by the same age of 70 years.
- The ladies <2% develop ovarian cancer by the age of 70 years.
- BRCA gene also gives increased susceptibility to ovarian cancer.
Mechanism: These genes encode tumor suppressor protein.
- So any change or mutation in the gene may inhibit or retard its suppressor function leading to uncontrolled cell proliferation.
- BRCA1 gene mutation also has increased the incidence of ovarian cancer.
- 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.
- 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%.
- Another source:
- By the age of 70 years:
- In 100 women without BRCA 1/2, around 7 women will get breast cancer.
- In 100 women with positive BRCA 1/2, around 45 to 65 will get breast cancer.
- By the age of 70 years:
Screening of the ladies with BRCA gene mutation:
- Ladies need transvaginal ultrasound 6 to 12 months.
- 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
- This is called the breast cancer gene.
- This gene is located on chromosome 17q.
- BRCA1 encodes for a protein which consists of 1863 amino acid.
- Breast cancer with BRCA1 has an exceptionally high proliferation rate.
- Breast cancer with BRCA1 has overexpression of p53.
- 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
- This is called the breast cancer gene.
- BRCA2 is located on chromosome 13q12-13.
- BRCA2 also has a higher proliferation than BRCA negative cases.
- Mutation of BRCA1 and BRCA2 found in individuals with a family history of breast cancer.
- Mutation in one of these genes carrying women may develop breast cancer or ovarian cancer.