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Introduction: AIB1, located at 20q12, is a member of the steroid hormone coactivator family. It contains a glutamine repeat (CAG/CAA) polymorphism at its carboxyl-terminal region that may alter the transcriptional activation of the receptor and affect susceptibility to breast cancer through altered sensitivity to hormones., Methods: We evaluated this repeat polymorphism in the context of early-onset disease by conducting a case-control study of 432 Australian women diagnosed with breast cancer before the age of 40 years and 393 population-based control individuals who were frequency matched for age. Genotyping was performed using a scanning laser fluorescence imager., Results: There were no differences in genotype frequencies between cases and control individuals, or between cases categorized by family history or by BRCA1 and BRCA2 germline mutation status. There was no evidence that the presence of one or two alleles of 26 glutamine repeats or fewer was associated with breast cancer (odds ratio = 1.03, 95% confidence interval = 0.73-1.44), or that women with alleles greater than 29 repeats were at increased risk of breast cancer. Exclusion of women who carried a BRCA1 or BRCA2 mutation (24 cases) and non-Caucasian women (44 cases) did not alter the risk estimates or inferences. We present raw data, including that on mutation carriers, to allow pooling with other studies., Conclusion: There was no evidence that risk of breast cancer depends on AIB1 CAG/CAA polymorphism status, even if affected women carry a mutation in BRCA1 or BRCA2.

The HER2 gene controls cellular function and has prognostic significance in breast cancer. The I655V polymorphism was associated with increased risk of breast cancer in Chinese women under the age of 45 years and in women with a first-degree family history of the disease. These associations, however, have not been confirmed in several studies of older women. We conducted a population-based case-control-family study of the I655V polymorphism using 409 Australian women with breast cancer diagnosed before the age of 40 years and 299 controls frequency matched for age. The I655V polymorphism was more common in cases (P = 0.01). A recessive model, in which homozygotes were associated with an adjusted odds ratio of 2.8 (95% confidence interval 1.3-6.2; P = 0.005), gave the best fit under parsimony. Although the biological role of the I655V polymorphism is not known, large independent studies of early onset breast cancer are warranted to attempt to replicate this finding.