AIB1 polymorphisms with breast cancer susceptibility: a pooled analysis of variation in BRCA1/2 mutation carriers and non-carriers.
The AIB1 gene (amplified in breast cancer 1), coding for a member of steroid receptor co-activator p160 protein family is involved in regulation of estrogen receptor transactivation influencing the estrogen-dependent gene expression. It contains a glutamine repeat polymorphism and several single nucleotide polymorphisms that may alter the transcriptional activation of the receptor and affect susceptibility to breast cancer. Previous studies have shown that these polymorphisms may modify the breast cancer risk in women carrying BRCA1/2 mutations. However, the results remained controversial. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 22 studies were identified, including 3,742 cases and 3,491 controls for AIB1 polyglutamine repeat polymorphism, 2,170 cases and 3,309 controls for Q586H polymorphism, and 2,183 cases and 3,319 controls for T960T polymorphism. Overall, we found no evidence of association for individuals who carried at least one AIB1 allele of 28 or 29 or more repeat with breast cancer risk. But we found increased breast cancer risk in BRCA1/2 mutation carriers for individuals with both alleles ≥29 polyglutamine repeat (OR, 1.64; 95% CI 1.24-2.17). And reduced risk was found to be associated with the Q586H polymorphism among the variant homozygote genotype carriers (OR, 0.42; 95% CI 0.23-0.77). Our results do not support the direct association of AIB1 polyglutamine repeat length and breast cancer. However, we found that BRCA1/2 mutation carriers with both alleles ≥29 repeats have a higher risk of breast cancer.
College of Pharmacy, Jinan University, Guangzhou, China. ebmmedicine@gmail.com
Ying
Y
Zhang
Meiyan
M
Huang
Zhenglan
Z
Zhu
D019943:Amino Acid Substitution; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3