title: Polymorphisms in the carcinogen detoxification genes CYB5A and CYB5R3 and breast cancer risk in African American women.
abstract: OBJECTIVE
  Cytochrome b 5 (encoded by CYB5A) and NADH cytochrome b 5 reductase (encoded by CYB5R3) detoxify aromatic and heterocyclic amine mammary carcinogens found in cigarette smoke. We hypothesized that CYB5A and CYB5R3 polymorphisms would be associated with breast cancer risk in women.
  
  
  METHODS
  We characterized the prevalence of 18 CYB5A and CYB5R3 variants in genomic DNA from African American (AfrAm) and Caucasian (Cauc) women from the Carolina Breast Cancer Study population (1,946 cases and 1,747 controls) and determined their associations with breast cancer risk, with effect modification by smoking.
  
  
  RESULTS
  A CYB5R3 variant, I1M+6T (rs8190370), was significantly more common in breast cancer cases (MAF 0.0238) compared with controls (0.0169, p = 0.039); this was attributable to a higher MAF in AfrAm cases (0.0611) compared with AfrAm controls (0.0441, p = 0.046; adjusted OR 1.41, CI 0.98-2.04; p = 0.062). When smoking was considered, I1M+6T was more strongly associated with breast cancer risk in AfrAm smokers (adjusted OR 2.10, 1.08-4.07; p = 0.028) compared with never smokers (OR = 1.21; 0.77-1.88; p for interaction = 0.176). I1M+6T and three additional CYB5R3 variants, -251T, I8-1676C, and *392C, as well as two CYB5A variants, 13G and I2-992T, were significantly more common in AfrAms compared with Caucs.
  
  
  CONCLUSIONS
  CYB5R3 I1M+6C>T should be considered in future molecular epidemiologic studies of breast cancer risk in AfrAms. Further, variants in CYB5A and CYB5R3 should be considered in the evaluation of other tumors in AfrAms that are associated with aromatic and heterocyclic amine exposures, to include prostate, bladder, and colon cancers.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI, 53706-1102, USA.
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Blanke
authors.forename: James C
authors.initials: JC
authors.lastname: Sacco
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.forename: Jingchun
authors.initials: J
authors.lastname: Luo
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Trepanier
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D002273:Carcinogens / Q000633:toxicity; D016022:Case-Control Studies; D042966:Cytochrome-B(5) Reductase / Q000235:genetics*; D015786:Cytochromes b5 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009657:North Carolina / Q000453:epidemiology; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D055815:Young Adult
chemical_list: C000594834:CYB5A protein, human; D002273:Carcinogens; D015786:Cytochromes b5; C583417:CYB5R3 protein, human; D042966:Cytochrome-B(5) Reductase