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Differential Association of Cytochrome P450 3A4 Genotypes With Onsets of Breast Tumors in African American Versus Caucasian Patients
  1. D. Olga McDaniel, MT, PhD*†,
  2. Tonya Thurber, MD*,
  3. Angela Lewis-Traylor, MD,
  4. Crystal Berry, MD*,
  5. William Henry Barber, MD, DPhil*†,
  6. Xinchun Zhou, MD, PhD,
  7. Steven Bigler, MD*‡,
  8. Ralph Vance, MD
  1. From the *School of Medicine, Departments of †Surgery, ‡Pathology, and §Medicine, University of Mississippi Medical Center, Jackson, MS.
  1. Received July 11, 2010, and in revised form May 20, 2011.
  2. Accepted for publication May 23, 2011.
  3. Reprints: D. Olga McDaniel, MT, PhD, University of MS Medical Center, 2500 N State St, CSB L-126, Jackson, MS 39216-4505. E-mail: omcdaniel{at}
  4. This study was in part was funded by American Cancer Society Intramural Grant, University of Mississippi Medical Center.


Introduction Malignant breast tumors are often hormone-dependent, and to this end, both estrogen and progesterone receptors are good prognostic markers for evaluation of the outcomes after therapy. In addition, HER-2/neu, whose expression is increasingly being associated with poor prognosis of breast cancer, has predictive potential after immunotherapy. Cytochrome P450 3A4 is highly involved in the metabolism of steroids. Thus, we investigated the impact of CYP 3A4 gene variants in association with clinical outcomes in African American (AFAM) versus Caucasian (CAU) patients with breast cancer diagnosis.

Methods Patients who had undergone biopsy procedures for diagnosis or for partial or radical mastectomy were recruited. The CYP 3A4 genotypes (A or G) were detected using polymerase chain reaction amplification and primers designed for a single nucleotide polymorphism. The messenger RNA (mRNA) transcripts were screened by reverse transcription-polymerase chain reaction. Clinical data including tumor staging, pathology grades, and family history were evaluated.

Results Frequency of the CYP 3A4-G (mutated variant) was significantly increased in AFAM patients as compared with controls (P < 0.001). No statistically significant difference was observed between the genotypes comparing the benign versus ductal carcinomas in situ (DCIS) or infiltrating ductal carcinomas (IDCAs). In AFAM patients, GG alleles were increased in IDCA with stage III tumors, and in CAU patients, the AA alleles were increased with stage III tumors. The mRNA expression was reduced in patients with IDCA versus DCIS or benign tumors (benign vs IDCA, P < 0.0009; DCIS vs IDCA, P < 0.005), as well in HER-2/neu-positive tumors versus samples negative for receptors (P < 0.0024).

Conclusions Genotype association was affected by race. Expression levels of total CYP 3A4 mRNA were inversely correlated with clinical diagnosis. This may suggest mRNA testing as an additional tool that accelerates improvement in the diagnosis of the onsets of breast cancer.

Key Words
  • African Americans
  • Caucasians
  • CYP 3A4 genotypes
  • breast cancer
  • receptors

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