UT Southwestern researchers are unlocking the secrets of breast cancer through an unusual source: mitochondrial DNA. 

Mitochondria, which produce the molecules that power our cells, are passed down to children from their mothers. In new research, UT scientists are using mitochondrial DNA to track patients’ ancestry to find out why they have a higher risk of breast cancer.

UT Southwestern surgery professor Roshni Rao said that by sequencing mitochondrial DNA, or mtDNA, her team was able to detect genetic differences from over 150,000 years of human migration. They then used this knowledge to identify the geographic origins of patients’ maternal ancestors.

“Usually when we think about DNA, we think about nuclear DNA, where you get half from your mother and half from your father,” Rao said. “Mitochondrial DNA is different because it is inherited only from your mother and passes along through the maternal line.”

The study looked at the mtDNA of 92 women from different ethnic backgrounds who currently have or have had a type of breast cancer called triple-negative breast cancer. Rao said triple-negative breast cancer is especially hard to treat because it does not have hormonal targets like some other cancers.

Alisa Cirina, manager at The Breast Center at St. David’s Medical Center, said physicians use family history to assess risk for patients.

“The reason we do that is because there is a hereditary component or a mutation in some gene that causes an increase [in cancer risk],” Cirina said. “When genetic testing is performed on a patient, what they’re doing is they’re identifying genes where maybe there’s a mutation or an issue.”

Many hereditary types of breast cancer are caused by specific mutations on the BRCA1 and BRCA2 genes, Cirina said. These genes make proteins that repair damaged DNA, stopping the cell from becoming cancerous. Mutations on these genes can be passed from parents to offspring and can increase the risk of breast and other types of cancer.

“Those [women with mutations on the BRCA1 or BRCA2 genes] are at a higher risk or likelihood to get breast cancer or ovarian cancer, so to get them screened ahead of time and to identify that is important, because that would change their screening and breast health program,” Cirina said. “It doesn’t decrease your risk, but it would improve detection.”

Genetic breast cancer risk factors can be higher for people with certain ethnic backgrounds. Cirina said that people with Ashkenazi Jewish, or Eastern European Jewish, heritage have increased instances of the BRCA1 and BRCA2 gene mutations, and Rao said triple-negative breast cancer is more common in African-American and Hispanic women.

The researchers found there was a discrepancy in 13 percent of the patients between their self-reported ethnic backgrounds and the ancestry found through mtDNA sequencing. 

Three of the patients discovered they were of Nigerian ancestry, a group the study found was genetically overrepresented among the African-American triple-negative breast cancer study participants. Another had previously unknown Ashkenazi Jewish ancestry.

“It is important to recognize that the American population in particular has a lot of admixture, and you may have a different ethnicity than you realize,” Rao said.

According to the study, patients must self-report their ethnic background during screenings and treatment. This can often be inaccurate because many Americans are unaware of parts of their ancestry that could lead to a higher risk of hereditary cancer, the study said.

Genetic testing and analysis of mtDNA is more accurate than self-reporting and can help better identify this ancestry identified with breast cancer risks, according to the study. This could improve outcomes of cancer and treatments, Rao said.

“It opens up a whole new area of research, in that we need to not only look at the tumor, but also what’s going on in that patient that may have predisposed to this type of breast cancer,” Rao said. “As we start to recognize the implications of different types of mitochondrial DNA patterns, we may realize that this could become a more standard part of a patient’s evaluation.”

This story has been updated since its initial publication. Alisa Cirina is a manager at the Breast Center, not a breast cancer nurse navigator.