|Title||Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Rotunno, M, Sun, X, Figueroa, J, Sherman, ME, Garcia-Closas, M, Meltzer, P, Williams, T, Schneider, SSmith, D Jerry, J, Yang, XR, Troester, MA|
|Journal||Breast Cancer Res|
|Date Published||2014 Jul 08|
|Keywords||Adolescent, Adult, Aged, Breast Neoplasms, Case-Control Studies, Cluster Analysis, Female, Gene Expression Profiling, Humans, Middle Aged, Odds Ratio, Parity, Pregnancy, Receptors, Estrogen, Risk Factors, Transcriptome, Young Adult|
INTRODUCTION: Relationships of parity with breast cancer risk are complex. Parity is associated with decreased risk of postmenopausal hormone receptor-positive breast tumors, but may increase risk for basal-like breast cancers and early-onset tumors. Characterizing parity-related gene expression patterns in normal breast and breast tumor tissues may improve understanding of the biological mechanisms underlying this complex pattern of risk.
METHODS: We developed a parity signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) patients (54 nulliparous and 76 parous). This parity signature, together with published parity signatures, was evaluated in gene expression data from 150 paired tumors and adjacent benign breast tissues from the Polish Breast Cancer Study, both overall and by tumor estrogen receptor (ER) status.
RESULTS: We identified 251 genes significantly upregulated by parity status in RM patients (parous versus nulliparous; false discovery rate = 0.008), including genes in immune, inflammation and wound response pathways. This parity signature was significantly enriched in normal and tumor tissues of parous breast cancer patients, specifically in ER-positive tumors.
CONCLUSIONS: Our data corroborate epidemiologic data, suggesting that the etiology and pathogenesis of breast cancers vary by ER status, which may have implications for developing prevention strategies for these tumors.
|Alternate Journal||Breast Cancer Res|
|PubMed Central ID||PMC4227137|
|Grant List||P30 ES010126 / ES / NIEHS NIH HHS / United States |
P50 CA058223 / CA / NCI NIH HHS / United States
R01 CA138255 / CA / NCI NIH HHS / United States
Z01 CP004410-31 / / Intramural NIH HHS / United States
U01 ES019472 / ES / NIEHS NIH HHS / United States
Veterinary and Animal Sciences