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Differential Patterns of Risk Factors for Early-Onset Breast Cancer by ER Status in African American Women.

ABSTRACT: Given the disproportionately high incidence of early-onset breast cancer and aggressive subtypes, such as estrogen receptor (ER)-negative tumors, in African American (AA) women, elucidation of risk factors for early onset of specific subtypes of breast cancer is needed.We evaluated associations of reproductive, anthropometric, and other factors with incidence of invasive breast cancer by age at onset (<45, ?45) in 57,708 AA women in the prospective Black Women's Health Study. From 1995 to 2013, we identified 529 invasive breast cancers among women <45 years of age (151 ER-, 219 ER+) and 1,534 among women ?45 years (385 ER-, 804 ER+). We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) for associations by age and ER status.Higher parity, older age at first birth, never having breastfed, and abdominal adiposity were associated with increased risk of early-onset ER- breast cancer: HRs were 1.71 for ?3 births versus one birth; 2.29 for first birth after age 25 versus <20 years; 0.61 for ever having breastfed versus never; and 1.64 for highest versus lowest tertile of waist-to-hip ratio. These factors were not associated with ER- cancer in older women or with ER+ cancer regardless of age.Differences in risk factors by ER subtype were observed for breast cancer diagnosed before the age of 45 years.Etiological heterogeneity by tumor subtype in early-onset breast cancer, in combination with a higher prevalence of the risk factors in AA women, may explain, in part, racial disparities in breast cancer incidence. Cancer Epidemiol Biomarkers Prev; 26(2); 270-7. ©2016 AACR.

SUBMITTER: Bertrand KA

PROVIDER: S-EPMC5296374 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Differential Patterns of Risk Factors for Early-Onset Breast Cancer by ER Status in African American Women.

Bertrand Kimberly A KA Bethea Traci N TN Adams-Campbell Lucile L LL Rosenberg Lynn L Palmer Julie R JR

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20161018 2

<h4>Background</h4>Given the disproportionately high incidence of early-onset breast cancer and aggressive subtypes, such as estrogen receptor (ER)-negative tumors, in African American (AA) women, elucidation of risk factors for early onset of specific subtypes of breast cancer is needed.<h4>Methods</h4>We evaluated associations of reproductive, anthropometric, and other factors with incidence of invasive breast cancer by age at onset (<45, ≥45) in 57,708 AA women in the prospective Black Women' ...[more]

PMID: 27756774

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Project description:Aggressive high-grade, estrogen receptor negative (ER-) breast cancer is more common among American women of African ancestry (AA) than those of European ancestry (EA). Epigenetic mechanisms, particularly DNA methylation and altered microRNA (miRNA) expression, may contribute to racial differences in breast cancer. However, few studies have specifically characterized genome-wide DNA methylation-based modifications at the miRNA level in relation to ER+ and ER- subtype, and their functional role in the regulation of miRNA expression, especially among high risk AA women. In this study, we evaluated DNA methylation patterns of miRNA encoding genes and their effect on expression in breast tumors from both AA and EA women. The genome-wide methylation screen identified a total of 7,191 unique CpGs mapped to 1,292 miRNA genes, corresponding to 2,035 unique mature miRNAs. We identified differentially methylated loci (DMLs: (|delta β|)>0.10, FDR<0.05) between ER- and ER+ tumor subtypes, including 290 DMLs shared in both races, 317 and 136 were specific to AA and EA women, respectively. Integrated analysis identified certain DMLs whose methylation levels were significantly correlated with the expression of relevant miRNAs, such as multiple CpGs within miR-190b and miR-135b highly negatively correlated with their expression. These results were then validated in the TCGA dataset. Target prediction and pathway analysis showed that these DNA methylation-dysregulated miRNAs are involved in multiple cancer-related pathways, including cell cycle G1-S growth factor regulation, cytoskeleton remodeling, angiogenesis, EMT, and ESR1-mediated signaling pathways. In summary, our results suggest that DNA methylation changes within miRNA genes are associated with altered miRNA expression, which may contribute to the network of subtype- and race-related tumor biological differences in breast cancer. These findings support the involvement of epigenetic regulation of miRNA expression and provide insights into the relations of clinical-relevant miRNAs to their target genes, which may serve as potential preventative and therapeutic targets.

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Differential Patterns of Risk Factors for Early-Onset Breast Cancer by ER Status in African American Women.

Publications

Differential Patterns of Risk Factors for Early-Onset Breast Cancer by ER Status in African American Women.

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