The risk of breast cancer transiently increases immediately following pregnancy. Hispanic women have one of the highest rates of postpartum breast cancers of all racial/ethnic minority groups in the US. The biology that underlies this risk window and the effect on the natural history of the disease is unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to be dysregulated in breast cancer. In this study, we measured the miRNA expression of 56 tumors from a case series of multiparous Hispanic women and assessed the pattern of expression by time since last full-term pregnancy. A data-driven splitting analysis on the pattern of 355 miRNAs separated the case series into two groups: a) an early group representing women diagnosed with breast cancer ≤ 5.2 years postpartum (n=12), and b) a late group representing women diagnosed with breast cancer ≥ 5.3 years postpartum (n=44). We identified 15 miRNAs that are differentially expressed between the early and late postpartum groups; 60% of these miRNAs are encoded on the X chromosome. Ten miRNAs had a two-fold or higher difference in expression; miR-138, miR-660, miR-31, miR-135b, miR-17, miR-454, and miR-934 were overexpressed in the early versus the late group; while miR-892a, miR-199a-5p, and miR-542-5p were under expressed in the early versus the late postpartum group. The DNA methylation of three out of five tested miRNAs (miR-31, miR-135b, and miR-138) was lower in the early versus late postpartum group, and negatively correlated with miRNA expression. Taken together, the results of this study show that miRNAs are differentially expressed and differentially methylated between tumors of the early versus late postpartum, suggesting that potential differences in epigenetic dysfunction may be operative in postpartum breast cancers.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/603490 |
| Date | January 2015 |
| Creators | Muñoz-Rodríguez, José Luis |
| Contributors | Futscher, Bernard W., Futscher, Bernard W., Klimecki, Walter T., Martinez, Maria Elena, Wondrak, Georg T. |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | en_US |
| Detected Language | English |
| Type | text, Electronic Dissertation |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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