Effects of HER2 genetic polymorphisms on its protein expression in breast cancer

Background and purposes: HER2 protein expression has been considered to be an important prognostic factor in breast cancer patients. Although the molecular mechanism of HER2 protein expression is currently unknown, single nucleotide polymorphisms (SNPs) of the HER2 gene may have some effects on its own expression. Here, we performed a trial to study the association between HER2 genetic polymorphisms and its protein expression in breast cancer.

Methods: Three SNPs in the HER2 gene were genotyped in 303 breast cancer patients using the Sequenom Mass ARRAY system. HER2 protein expression, ER, PR, P53, and Ki67 status was detected by immunohistochemistry. A Pearson's chi-square test was used to analyze the associations of the polymorphisms with its protein expression, corresponding with clinicopathological characteristics of breast cancer.

Results: Under the codominant model, rs1058808 and rs2517956 polymorphisms were associated with HER2 protein expression in breast cancer (p=0.007; p=0.008, respectively). For SNP rs1058808, patients with genotypes CG and GG were more likely to have high HER2 protein expression than patients with genotype CC (p=0.007). No significant associations could be found between the three SNPs and breast cancer patients' clinical stage, tumor size, histological grade, lymph node metastasis, ER, PR, Ki67 and P53 status (p>0.05).

Conclusions: HER2 rs1058808 and rs2517956 polymorphisms are associated with its protein expression in breast cancer. Our study might provide new insights into the mechanisms of HER2 protein expression.