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

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.