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Objectives  We carried out a meta-analysis focusing on the relationship between length of AIB1 gene poly-Q repeat domain as a modifier of breast cancer (BC) susceptibility in patients with BRCA1 and BRCA2 mutation carriers.    Data sources  We searched MEDLINE and EMBASE for all medical literature published until February, 2012.    Study Eligibility criteria  Studies were included in the meta-analysis if they met all the predetermined criteria, such as: (a) case-control or cohort studies; (b) the primary outcome was clearly defined as BC; (c) the exposure of interest measured was AIB1 polyglutamine repeat length genotype; (d) provided relative risk (RR) or odds ratio (OR) estimates and their 95% confidence intervals (CIs).    Synthesis methods  Two of the authors independently evaluated the quality of the studies included and extracted the data. Meta-analyses were performed for case-control and cohort studies separately. Heterogeneity was examined and the publication bias was assessed with a funnel plot for asymmetry.    Result  7 studies met our predetermined inclusion criteria and were included in the meta-analysis. Overall quality ratings of the studies varied from 0.36 to 0.77, with a median of 0.5. The overall RR estimates of 29/29 poly-Q repeats on risk of BC in BRCA1/2, BRCA1, and BRCA2, were always greater than 1.00; however, this effect was not statistically significant. In the meta-analysis of studies reporting the effect of 28/28 poly-Q repeats on risk of BC in BRCA1/2, BRCA1, and BRCA2, the overall RR decreased below 1.00; however, this effect was not statistically significant. Similar estimates were shown for at least 1 allele of ≤26 repeats.    Conclusions  Genotypes of AIB1 polyglutamine polymorphism analyzed do not appear to be associated to a modified risk of BC development in BRCA1 and BRCA2 mutation carriers. Future research on length of poly-Q repeat domain and BC susceptibility should be discouraged and more promising potential sources of penetrance variation among BRCA1 and BRCA2 mutation carriers should be investigated.

Polymorphic Repeat Length in the AIB1 Gene and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Meta-Analysis of Observational Studies