title: Differential association of cytochrome P450 3A4 genotypes with onsets of breast tumors in African American versus Caucasian patients.
abstract: BACKGROUND
  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.
authors.affiliation: School of Medicine, Department of Surgery, University of Mississippi Medical Center, Jackson, MS, USA. omcdaniel@umc.edu
authors.forename: D Olga
authors.initials: DO
authors.lastname: McDaniel
authors.forename: Tonya
authors.initials: T
authors.lastname: Thurber
authors.forename: Angela
authors.initials: A
authors.lastname: Lewis-Traylor
authors.forename: Crystal
authors.initials: C
authors.lastname: Berry
authors.forename: William Henry
authors.initials: WH
authors.lastname: Barber
authors.forename: Xinchun
authors.initials: X
authors.lastname: Zhou
authors.forename: Steven
authors.initials: S
authors.lastname: Bigler
authors.forename: Ralph
authors.initials: R
authors.lastname: Vance
mesh_terms: D000328:Adult; D001741:Black or African American; D000483:Alleles; D001706:Biopsy; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D044465:White People
chemical_list: D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013256:Steroids; D051544:Cytochrome P-450 CYP3A