title: Lipid metabolism genes in contralateral unaffected breast and estrogen receptor status of breast cancer.
abstract: Risk biomarkers that are specific to estrogen receptor (ER) subtypes of breast cancer would aid the development and implementation of distinct prevention strategies. The contralateral unaffected breast of women with unilateral breast cancer (cases) is a good model for defining subtype-specific risk because women with ER-negative (ER-) index primaries are at high risk for subsequent ER-negative primary cancers. We conducted random fine needle aspiration of the unaffected breasts of cases. Samples from 30 subjects [15 ER-positive (ER+) and 15 ER- cases matched for age, race and menopausal status] were used for Illumina expression array analysis. Findings were confirmed using quantitative real-time PCR (qRT-PCR) in the same samples. A validation set consisting of 36 subjects (12 ER+, 12 ER- and 12 standard-risk healthy controls) was used to compare gene expression across groups. ER- case samples displayed significantly higher expression of 18 genes/transcripts, 8 of which were associated with lipid metabolism on gene ontology analysis (GO: 0006629). This pattern was confirmed by qRT-PCR in the same samples, and in the 24 cases of the validation set. When compared to the healthy controls in the validation set, significant overexpression of 4 genes (DHRS2, HMGCS2, HPGD and ACSL3) was observed in ER- cases, with significantly lower expression of UGT2B11 and APOD in ER+ cases, and decreased expression of UGT2B7 in both subtypes. These data suggest that differential expression of lipid metabolism genes may be involved in the risk for subtypes of breast cancer, and are potential biomarkers of ER-specific breast cancer risk.
authors.affiliation: Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Denise
authors.initials: D
authors.lastname: Scholtens
authors.forename: Michelle
authors.initials: M
authors.lastname: Holko
authors.forename: David
authors.initials: D
authors.lastname: Ivancic
authors.forename: Oukseub
authors.initials: O
authors.lastname: Lee
authors.forename: Hong
authors.initials: H
authors.lastname: Hu
authors.forename: Robert T
authors.initials: RT
authors.lastname: Chatterton
authors.forename: Megan E
authors.initials: ME
authors.lastname: Sullivan
authors.forename: Nora
authors.initials: N
authors.lastname: Hansen
authors.forename: Kevin
authors.initials: K
authors.lastname: Bethke
authors.forename: Carola M
authors.initials: CM
authors.lastname: Zalles
authors.forename: Seema A
authors.initials: SA
authors.lastname: Khan
mesh_terms: D000328:Adult; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen