Testing Positive for Less Common Gene Abnormalities

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Genetic tests can determine if someone has an abnormal BRCA1 or BRCA2 gene. Changes in other genes are also associated with breast cancer. These abnormal genes are much less common and don't seem to increase risk as much as abnormal BRCA1 and BRCA2 genes, which are considered rare. Still, because these genetic mutations are more rare, they haven't been studied as much as the BRCA genes.

A genetic counselor may order testing for the following abnormal genes: ATM, BRIP1, CDH1, CHEK2, MRE11A, NBN, PALB2, PTEN, RAD50, RAD51C, STK11, or TP53. These genes can be tested individually or as part of a larger gene panel that includes BRCA1 and BRCA2 if it's determined from your personal or family history that these tests are an option. Right now, there is not a clinical test for an abnormal SEC23B gene.

Here are the details about each of the above-mentioned genes and the abnormal versions of these genes:

  • ATM: The ATM gene helps repair damaged DNA. DNA carries genetic information in cells. Inheriting two abnormal copies of this gene causes the disease ataxia-telangiectasia, a rare disease that affects brain development. Inheriting one abnormal ATM gene has been linked to an increased rate of breast cancer and pancreatic cancer in some families because the abnormal gene stops the cells from repairing damaged DNA.
  • BRIP1: The BRIP1 gene also works to repair DNA. Inheriting one abnormal BRIP1 gene is associated with higher risk of both breast and ovarian cancer.
  • CDH1: The CDH1 gene makes a protein that helps cells bind together to form tissue. An abnormal CDH1 gene increases the risk of a rare type of stomach cancer at an early age. The lifetime risk is up to 83%. Women with an abnormal CDH1 gene also have a 39% to 52% lifetime risk of invasive lobular breast cancer.
  • CHEK2: The CHEK2 gene provides instructions for making a protein that stops tumor growth. An abnormal CHEK2 gene can at least double breast cancer risk, double colon cancer risk, and increase prostate cancer risk.
  • MRE11A: Along with the RAD50 and NBN genes, the MRE11A gene forms the MRN complex, which helps repair DNA damage in cells. An abnormal MRE11A gene is linked to ataxia-telangiectasia-like disorder, a rare disease that affects brain development. The disease also weakens the immune system and increases cancer risk.
  • NBN: Along with the MRE11A and RAD50 genes, the NBN gene forms the MRN complex, which helps repair DNA damage in cells. An abnormal NBN gene causes Nijmegen breakage syndrome, a condition that causes slow growth in infancy and early childhood. People with Nijmegen breakage syndrome are shorter than average; have a higher risk of several types of cancer, including breast cancer; and many other health problems. Of the three genes in the MRN complex, researchers think that an abnormal NBN gene has the strongest link to breast cancer.
  • PALB2: The PALB2 gene is called the partner and localizer of BRCA2. It provides instructions to make a protein that works with the BRCA2 protein to repair damaged DNA and stop tumor growth. Research published in 2014 found that an abnormal PALB2 gene increases breast cancer risk 5 to 9 times higher than average, almost as high as an abnormal BRCA1 or BRCA2 gene. Women with an abnormal PALB2 gene have a 33% to 58% lifetime risk of developing breast cancer. In comparison, women with an abnormal BRCA1 gene have a 50% to 70% risk of developing breast cancer by age 70. Women with an abnormal BRCA2 gene have a 40% to 60% risk of developing breast cancer by age 70.
  • PTEN: The PTEN gene helps regulate cell growth. An abnormal PTEN gene causes Cowden syndrome, a rare disorder in which people have a higher risk of both benign (not cancer) and cancerous breast tumors, as well as growths in the digestive tract, thyroid, uterus, and ovaries. The lifetime breast cancer risk for women with a PTEN mutation is up to 85%.
  • RAD50: Along with the MRE11A and NBN genes, the RAD50 gene forms the MRN complex, which helps repair DNA damage in cells. An abnormal RAD50 gene has been linked to a higher risk of breast cancer in some families because the abnormal gene stops the cells from repairing damaged DNA.
  • RAD51C: The RAD51C gene repairs DNA damage. People who have inherited one abnormal copy have higher risk of breast and ovarian cancer.
  • SEC23B: In 2015, an abnormal version of the SEC23B gene also was linked to Cowden syndrome. The SEC23B gene also helps regulate cell growth. Because this discovery is so new, there is not a clinical test available for an abnormal SEC23B gene.
  • STK11: The STK11 gene helps regulate cell growth. An abnormal STK11 gene causes Peutz Jegher syndrome, a rare disorder in which people tend to develop a type of polyp, called a hamartomatous polyp, mostly in the small intestine but also in the stomach and colon. People with Peutz Jegher syndrome are at higher risk not only of gastrointestinal cancers, but also breast and lung cancer and ovarian tumors. People may also develop freckling around the eyes, nose, and mouth, as well as inside the mouth.
  • TP53: The TP53 gene provides instructions to the body for making a protein that stops tumor growth. Inheriting an abnormal TP53 gene causes Li-Fraumeni syndrome, a disorder that causes people to develop soft tissue cancers at a young age. People with this rare syndrome have a higher-than-average-risk of breast cancer and several other cancers, including leukemia, brain tumors, and sarcomas (cancer of the bones or connective tissue). The cancer risk in women with a TP53 mutation is up to nearly 100%. In men, it is up to 73%. This gender difference is mostly due to the high breast cancer risk in women.

Inheriting two abnormal copies of the BRCA2, BRIP1, MRE11A, NBN, PALB2, RAD50, or RAD51C genes causes the disease Fanconi anema, which suppresses bone marrow function and leads to extremely low levels of red blood cells, white blood cells, and platelets. People with Fanconi anemia also have a higher risk of several other types of cancer, including kidney cancer and brain cancer.

If you test positive for any of the above abnormal genes, your genetic counselor can advise you about possible next steps, including increased screening, risk-reducing hormonal therapy, or, in some cases, risk-reducing surgery.



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