Effects of HER2 genetic polymorphisms on its protein expression in breast cancer.
OBJECTIVE
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.
Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: dr_suyh@126.com.
Yonghui
Y
Su
Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: jiangyongdonghmu@126.com.
Yongdong
Y
Jiang
Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: sunshanshandabao@163.com.
Shanshan
S
Sun
Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: rickyyin1988@hotmail.com.
Huizi
H
Yin
Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: shanming@ems.hrbmu.edu.cn.
Ming
M
Shan
Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: twyssw@hotmail.com.
Weiyang
W
Tao
Department of Radiotherapy, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: gexiaofeng121@163.com.
Xiaofeng
X
Ge
Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China. Electronic address: pangdasir@163.com.
Da
D
Pang
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics
D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
Breast cancer; Gene polymorphism; HER2 gene; Protein expression