title: Estrogen receptor/progesterone receptor-negative breast cancers of young African-American women have a higher frequency of methylation of multiple genes than those of Caucasian women.
abstract: OBJECTIVE
  To provide a molecular rationale for negative prognostic factors more prevalent in African-American (AA) than Caucasian (Cau) women, we investigated the frequency of promoter hypermethylation in invasive ductal breast cancers in the two races.
  
  
  METHODS
  HIN-1, Twist, Cyclin D2, RAR-beta, and RASSF1A were analyzed in DNA from 67 AA and 44 Cau invasive ductal breast cancers, stratified by age and estrogen receptor/progesterone receptor (ER/PR) status, by methylation-specific PCR. Hierarchical multiple logistic regression analysis was applied to determine estimated probabilities of methylation. Expression of HIN-1 mRNA was analyzed by in situ hybridization and quantitative reverse transcribed PCR.
  
  
  RESULTS
  Significant differences between races were observed in the ER-/PR-, age < 50 subgroup; AA tumors had higher frequency of methylation (P < 0.001) in four of five genes as compared with Cau and also a higher prevalence (80 versus 0%; P < 0.005) of three or more methylated genes per tumor. No differences in gene methylation patterns were observed across the two races for ER+/PR+ tumors in all ages and ER-/PR- tumors in age > 50. ER+/PR+ status was associated with higher frequency of methylation in Cau tumors of all ages but only with the age > 50 subgroup in AA. Frequent Cyclin D2 methylation was significantly associated (P = 0.01) with shorter survival time.
  
  
  CONCLUSIONS
  ER-/PR-, age < 50 tumors in AA women, have a significantly higher frequency of hypermethylation than in those of Cau women. Comparative studies, such as these, could provide a molecular basis for differences in tumor progression and pathology seen in the two races.
authors.affiliation: Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Mehrotra
authors.forename: M Michelle
authors.initials: MM
authors.lastname: Ganpat
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Kanaan
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Fackler
authors.forename: Megan
authors.initials: M
authors.lastname: McVeigh
authors.forename: Jaana
authors.initials: J
authors.lastname: Lahti-Domenici
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Tammy
authors.initials: T
authors.lastname: Naab
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parmigiani
authors.forename: Carolyn
authors.initials: C
authors.lastname: Broome
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
mesh_terms: D044383:Black People / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence; D011960:Receptors, Estrogen / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone