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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2010

01-06-2010 | Epidemiology

A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk

Authors: Rongxi Yang, Bettina Schlehe, Kari Hemminki, Christian Sutter, Peter Bugert, Barbara Wappenschmidt, Juliane Volkmann, Raymonda Varon, Bernhard H. F. Weber, Dieter Niederacher, Norbert Arnold, Alfons Meindl, Claus R. Bartram, Rita K. Schmutzler, Barbara Burwinkel

Published in: Breast Cancer Research and Treatment | Issue 3/2010

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Abstract

MicroRNAs (miRNAs) regulate pathways involved in cell differentiation, proliferation, development, and apoptosis by degradation of target mRNAs and/or repression of their translation. Although the single nucleotide polymorphisms (SNPs) in miRNAs target sites have been studied, the effects of SNPs in miRNAs are largely unknown. In our study, we first systematically sequenced miRNA genes reported to be involved in breast cancer to identify/verify SNPs. We analyzed four SNPs, one located in the pre-miRNA and the other three located in miRNA flanking regions, for a putative association with breast cancer risk. The SNP rs895819, located in the terminal loop of pre-miRNA-27a, showed a protective effect. In a large familial breast cancer study cohort, the rare [G] allele of rs895819 was found to be less frequent in the cases than in the controls, indicating a reduced familial breast cancer risk ([G] vs. [A]: OR = 0.88, 95% CI 0.78–0.99, P = 0.0287). Furthermore, age stratification revealed that the protective effect was mainly observed in the age group < 50 years of age ([G] vs. [A]: OR = 0.83, 95% CI 0.70–0.98, P = 0.0314), whereas no significant effect was observed in the age group ≥ 50 years of age, indicating a possible hormone-related effect. It has been shown that artificial mutations in the terminal loop of miR-27a can block the maturation process of the miRNA. We hypothesize that the G-variant of rs895819 might impair the maturation of the oncogenic miR-27a and thus, is associated with familial breast cancer risk.
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Metadata
Title
A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk
Authors
Rongxi Yang
Bettina Schlehe
Kari Hemminki
Christian Sutter
Peter Bugert
Barbara Wappenschmidt
Juliane Volkmann
Raymonda Varon
Bernhard H. F. Weber
Dieter Niederacher
Norbert Arnold
Alfons Meindl
Claus R. Bartram
Rita K. Schmutzler
Barbara Burwinkel
Publication date
01-06-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-009-0633-5

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