title: Genome-wide methylation patterns provide insight into differences in breast tumor biology between American women of African and European ancestry.
abstract: American women of African ancestry (AA) are more likely than European-Americans (EA) to be diagnosed with aggressive, estrogen receptor (ER) negative breast tumors; mechanisms underlying these disparities are poorly understood. We conducted a genome wide (450K loci) methylation analysis to determine if there were differences in DNA methylation patterns between tumors from AA and EA women and if these differences were similar for both ER positive and ER negative breast cancer. Methylation levels at CpG loci within CpG islands (CGI)s and CGI-shores were significantly higher in tumors (n=138) than in reduction mammoplasty samples (n=124). In hierarchical cluster analysis, there was separation between tumor and normal samples, and in tumors, there was delineation by ER status, but not by ancestry. However, differential methylation analysis identified 157 CpG loci with a mean β value difference of at least 0.17 between races, with almost twice as many differences in ER-negative tumors compared to ER-positive cancers. This first genome-wide methylation study to address disparities indicates that there are likely differing etiologic pathways for the development of ER negative breast cancer between AA and EA women. Further investigation of the genes most differentially methylated by race in ER negative tumors can guide new approaches for cancer prevention and targeted therapies, and elucidate the biologic basis of breast cancer disparities.
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Allyson C
authors.initials: AC
authors.lastname: Young
authors.forename: Lara E
authors.initials: LE
authors.lastname: Sucheston
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hu
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
authors.forename: Carl D
authors.initials: CD
authors.lastname: Morrison
authors.forename: Kitaw
authors.initials: K
authors.lastname: Demissie
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Higgins
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D011960:Receptors, Estrogen