Mitochondrial DNA Reveals Patients’ Unexpected Ancestry – and Breast Cancer Risk

Mitochondrial DNA Reveals Patients’ Unexpected Ancestry – and Breast Cancer Risk

Analyses of mitochondrial DNA in women with triple-negative breast cancer revealed that a significant proportion of these patients may have a different ancestry than they are aware of — influencing their risk for more aggressive types of breast cancer.

Researchers also report the surprise finding that people stemming from Nigeria, Cameroon, and Sierre Leone are at particularly high risk for triple-negative breast cancer.

The findings, published in the study “Genetic Ancestry using Mitochondrial DNA in patients with Triple-negative breast cancer (GAMiT study),” in the journal Cancer, underscore mitochondrial DNA analyses could be used for risk stratification of patients.

Triple-negative breast cancer — the scientific name for breast tumors having no receptors for estrogen, progesterone, or HER2 — is more aggressive and difficult to treat than other types of breast cancer. The cancer is also more likely to spread, and patients’ chances of survival are generally lower than those with other forms of breast cancer.

Researchers know that people with an African-American or Ashkenazi Jewish ancestry have a higher risk of triple-negative breast cancer. Patients with this cancer subtype also tend to be younger, and thus commonly missed by mammography screenings, which target women over 50.

Since mitochondrial DNA is inherited only from the mother, no genetic mixing occurs, meaning it can be used to track ancestry. Researchers at the  University of Texas Southwestern Medical Center figured this information may also ultimately be used to assess breast cancer risk.

The GAMiT study investigated mitochondrial DNA and compared it to self-reported ancestry among women diagnosed with triple-negative breast cancer, particularly looking for unexpected mitochondrial DNA patterns.

The group consisted of 31 African-Americans, 31 Caucasians, and 30 Hispanics. Interestingly, 13 percent of the individuals were not aware of ancestry that could influence their risk for triple-negative breast cancer. The largest disagreement was found among patients reported to be Hispanic, where eight patients, amounting to 26 percent, had a non-Hispanic ancestry. Three of the women had Nigerian, and one had Ashkenazi Jewish, roots.

Researchers also discovered that self-reported Hispanic patients were youngest and had the largest tumor size. Although the risk of developing cancer is larger in some ethnic groups, the research team found no differences in outcomes such as surgery, lymph node metastases, or survival. Among the 30 Hispanic patients, eight had a family history of breast cancer, carrying mutations in the BRCA1 or BRCA2 genes.

“Some patients who self-identified as Hispanic had African-American ancestry. One Hispanic woman was found to be Ashkenazi Jewish,” Dr. Roshni Rao, an associate professor of surgery at the Harold C. Simmons Comprehensive Cancer Center and director of the George N. Peters M.D. Center for Breast Surgery at UT Southwestern, said in a news release.

“It is estimated that 10 to 30 percent of Americans may not be aware of their mixed ancestry. This type of assessment has the potential to be informative for other cancers where we see ethnic differences in frequency without understanding the cause,” added Dr. Barbara Haley, a professor of Internal Medicine, who holds the Charles Cameron Sprague, M.D., Chair in Clinical Oncology, and was the senior author of the study.

“If you know your ancestry, then you could be included in the group that gets screened at a younger age,” said Rao.