TY - JOUR
T1 - Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status
AU - Rotunno, Melissa
AU - Sun, Xuezheng
AU - Figueroa, Jonine
AU - Sherman, Mark E.
AU - Garcia-Closas, Montserrat
AU - Meltzer, Paul
AU - Williams, Tyisha
AU - Schneider, Sallie S.
AU - Jerry, D. J.
AU - Yang, Xiaohong R.
AU - Troester, Melissa A.
N1 - Funding Information:
This research was supported by the following programs and grants: the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health; a National Institute of Environmental Health Sciences and NCI grant from the Breast Cancer and the Environment Research Program (U01 ES019472); NCI grant R01 CA138255; and a Breast Specialized Program of Research Excellence (SPORE) grant to the University of North Carolina (P50 CA058223). The Avon Foundation is gratefully acknowledged for financial support of this work.
PY - 2014/7/8
Y1 - 2014/7/8
N2 - 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.
AB - 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.
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U2 - 10.1186/bcr3689
DO - 10.1186/bcr3689
M3 - Article
C2 - 25005139
AN - SCOPUS:84903807525
SN - 1465-5411
VL - 16
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - R74
ER -