Understanding Hereditary Breast and Ovarian Cancer Syndromes: the BRCA gene
Some women are at exceptionally high risk of developing breast and ovarian cancer because they carry a genetic mutation of the BRCA gene. The BRCA genes code for a protein that corrects mistakes in DNA. Without this protein, a woman (men carry it also) are at higher risk of developing breast and ovarian cancers. You may have heard that Angelina Jolie had bilateral mastectomies, and that her mother died at a young age of ovarian cancer. Gilda Radner also died at a very young age of ovarian cancer, as did many of her family members. Both carried the mutation in the BRCA gene.
How do you know if you carry this gene mutation?
The incidence of this mutation is 2.5% in Jewish people of Ashkenazi descent, vs. 0.2% in the general population. It is more common in Ashkenazi Jews because the original gene mutation came from Eastern Europe, and the Jewish population usually married within their community. Regardless, any nationality can carry this gene. Family history is of the utmost importance. Red flags are the following: multiple family members in multiple generations with breast and ovarian cancer, of if any one person has had breast cancer more than once, breast and ovarian cancers, breast cancer younger than 50, ovarian cancer at any age, and a male with breast cancer.
The significance of the BRCA gene:
The risk of breast cancer in the general population is 12% throughout your lifetime. If you carry the BRCA gene, your lifetime risk increases to 75-85%. That is 6-7 times more breast cancer in this population! Many of these cancers occur at a much earlier age than expected. In order to decrease mortality from breast cancer in BRCA carriers, doctors recommend that women who carry the gene begin mammograms yearly beginning at age 25. It is also recommended that these women also have a yearly MRI of the breasts. Along with it, surveillance with breast self-exams, and a physician exam twice yearly is a the recommended monitoring routine. There are medications such as tamoxifen and raloxifene that can decrease the risk of breast cancer and can be prescribed for those at high risk. Some women may elect to have a prophylactic mastectomy. This is a very personal decision.
The risk of ovarian cancer is also increased. The lifetime risk of ovarian cancer in the general population is 1.4%. If you carry the BRCA gene, your risk increases to 25-40%. Ovarian cancer is usually asymptomatic in its earliest stages, so women who carry the BRCA gene should have high risk ovarian cancer surveillance which includes clinical exams every 6 months, an ultrasound once or twice yearly, and a blood test, CA125, which is marker for breast cancer. Preventive, or prophylactic removal of the ovaries is recommended after childbearing is completed.
Inheritance of the BRCA gene
The BRCA gene is inherited by autosomal dominance. This means that you only need to inherit one copy of the gene from either your father or mother to demonstrate the inherited trait. The BRCA gene can be inherited from the maternal or paternal side of the family, so if your father's mother, aunts, sisters or cousins had a strong history of breast and ovarian cancer, and they are found to carry the BRCA gene, your father can inherit the gene and pass it to his sons and daughters. If any person, man or woman caries the BRCA gene, statistically he or she will pass it to 50% of her children.
How do I get tested?
Testing is very simple, and requires a blood or saliva sample. Genetic counselor are trained to assess risks and offer advice regarding appropriate tests. Many physicians also offer testing through their offices, often oncologists and gynecologists do this.
Many laboratories offer genetic testing now. The results indicate if the BRCA gene is present, or absent. Occasionally the result will indicate a mutation of uncertain significance. This means that there is a mutation, but the current databases are not able to determine with certainty that the mutation confers a higher risk of cancer. These mutations are monitored until the genetics community can eventually classify them as benign or deleterious (harmful). Most of them turn out to be insignificant. The information obtained from genetic testing provides information to manage the person who has the gene, offering high risk surveillance, risk-reducing medication, or prophylactic surgery. It is also important information for family members who wish to be tested.