title: Genetic Ancestry using Mitochondrial DNA in patients with Triple-negative breast cancer (GAMiT study).
abstract: BACKGROUND
  Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2)/neu receptors, and is aggressive and therapeutically challenging. Genetic ancestry testing is an emerging medical field. Mitochondrial DNA (mtDNA), which is distinct from nuclear DNA, is maternally inherited and allows for origin determination. Patients with TNBC tend to be younger and are more likely to be African American, making this an ideal disease for mtDNA exploration. To the authors' knowledge, the current study is the first to perform mtDNA for self-described African American, White, and Hispanic patients with TNBC to identify mtDNA patterns.
  
  
  METHODS
  Patients with TNBC who were at any stage of therapy/survivorship were included. Self-reported ethnicity was confirmed at the time of the prospective buccal swab. Haplogroup prediction was performed on sequencing of hypervariable region 1. Using sequence similarity scores and lineage databases, sequence patterns were determined. Data regarding presentation and treatment, tumor features, and outcomes was collected.
  
  
  RESULTS
  A total of 92 patients were included: 31 self-described African American, 31 White, and 30 Hispanic individuals. Hispanic patients were found to have the largest tumor size (4.5 cm; P = .01) and youngest age (41 years; P<.0001). Eight patients were BRCA1/2 mutation carriers. There were no differences noted among groups with regard to surgery, lymph node metastases, or survival. Analysis revealed Nigerian, Cameroon, or Sierra Leone ancestry and haplogroups A, U, H, or B to be the most common mtDNA patterns. Twelve discordances (13%) between mtDNA analysis and self-described ethnicity were identified among the 92 patients. The highest discordance (26%; 8 patients) was noted in self-described Hispanic patients: 3 had Nigerian ancestry, and 1 individual demonstrated haplogroup K mtDNA (Ashkenazi Jewish ancestry).
  
  
  CONCLUSIONS
  Discordance between self-reported ethnicity and mtDNA analysis was identified in 13% of patients with TNBC. The identification of mtDNA patterns with a predisposition toward TNBC may allow for risk stratification. Cancer 2017;107-113. © 2016 American Cancer Society.
authors: Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Roshni
authors: R
authors: Rao
authors: Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Aeisha
authors: A
authors: Rivers
authors: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Asal
authors: A
authors: Rahimi
authors: Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Rachel
authors: R
authors: Wooldridge
authors: Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Madhu
authors: M
authors: Rao
authors: Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Marilyn
authors: M
authors: Leitch
authors: Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland.
authors: David
authors: D
authors: Euhus
authors: Division of Medical Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Barbara B
authors: BB
authors: Haley
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D044383:Black People / Q000235:genetics; D002163:Cameroon; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008875:Middle Aged; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
keywords: African American; ethnicity; genetic ancestry; mitochondrial DNA; triple-negative breast cancer