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Learning about breast cancer risk from DNA

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One of the most important lists in medical genomics is the ACMG 59. Assembled by the American College of Medical Genetics and Genomics (ACMG), the 59 different health-related genes on this list serve as guidelines to help people avoid or mitigate potentially serious health complications that result from variants in these genes. The ACMG 59 list covers some of the most researched genes in scientific literature, yet many of them are unknown outside of the academic and medical communities. It’s rare for a gene to be elevated into public discussion, and even rarer for a gene’s importance to be highlighted by celebrities and world leaders. While each gene on the ACMG 59 is incredibly important, no other gene has captured the public eye quite like the BRCA genes.
The BRCA genes (there are two, BRCA1 and BRCA2) gained widespread attention in 2013 when actress Angelina Jolie wrote candidly about her family’s history of cancer, her decision to undergo a preventative double mastectomy, and the role genetic testing had in helping her reduce her risk of developing cancer in the future. Jolie learned that she had inherited a variant in the BRCA1 gene after her mother had died from ovarian cancer. Variants like the one that Jolie had inherited are known to significantly increase the risk of breast cancer: Women without a BRCA1 variant have a 12% risk of developing breast cancer at some point in their lives, while those with a BRCA1 variant have somewhere between a 46% and 87% chance of developing breast cancer.

Variants in the BRCA genes don’t just increase a person’s risk of breast cancer—they also can significantly increase the odds of developing cancer of the ovaries, prostate, or pancreas. However, simply because someone inherits one of these variants doesn’t guarantee that they will develop cancer. A person’s habits, their environment, and other genetic factors can all impact whether or not cancer develops.

Variants in BRCA genes have such a strong effect on cancer risk because these genes play an important role in protecting our DNA from cancer-causing mutations. In essence, cancer is a disease where cells in a person’s body go rogue and begin to duplicate themselves in an uncontrolled way. This happens when mutations develop in a person’s DNA that disable, or allow the cell to bypass, various security mechanisms that are in place to stop rogue cell duplication. One such mechanism is the action of BRCA proteins (proteins made from the BRCA genes).
BRCA proteins can be thought of as small aircraft carriers inside a cell, because their job is to carry other specialized DNA repair proteins to regions of the genome that have been damaged. If breaks in the DNA go unrepaired, or if they’re repaired incorrectly, it could result in disabling of a cell’s security system and progression towards cancer. The BRCA proteins help prevent this by bringing numerous different response proteins to the site of damage. However, when a person inherits variants in the BRCA genes that prevent them from producing their BRCA proteins, cells that depend on the BRCA “aircraft carriers” are less able to respond to DNA damage and are more likely to become cancerous.

There are ways to lessen the impact of cancer development and, potentially prevent it

Fortunately, there are steps that many people can take to potentially lessen the impact of cancer development and, in some cases, even prevent it. Men and women who test positive for BRCA variants are advised to be sure they know how to do a thorough breast-self exam, do them monthly, and inform their doctors of their genetic test results. Women can also screen more regularly with mammograms and breast MRIs (some men may choose to do these as well). A woman could take a medication like tamoxifen, which affects how estrogen works in the body, and can lower the odds of breast cancer. Or they could choose to have a preventative mastectomy—as Angelina Jolie did—with the option to have reconstructive surgery following the mastectomy. Ovarian cancer can be largely prevented by having the ovaries and fallopian tubes surgically removed, which is a relatively minor procedure, and is often done after childbearing years. It’s also advised that people talk to their relatives about their test results because these variants are heritable which means people who are genetically related may also benefit from genetic testing.
Whatever the result, genetic counselors are a great resource for helping you understand your testing options, results, and any increased risk of cancer that you and your family may have. Ultimately, genetic testing for BRCA variants gives us the power of knowledge and the opportunity to take potentially life-saving action. For this reason, BRCA genes have been included in the ACMG 59 list. If you’re interested in learning about your DNA and whether you’ve inherited variants in any of the ACMG 59 genes, Helix has partnered with PerkinElmer Genomics to provide ACMG 59 testing in the coming months, including the BRCA genes.

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For more information about screening, prevention, and treatment of breast cancer, see this expanded article and a list of common questions relating to breast cancer written by Misha Rashkin, a certified genetic counselor at Helix.