Single nucleotide polymorphisms and expression/amplification of HER2 in patients with breast cancer.

Abstract

1523 Background: Human Epithelial growth factor Receptor 2 (HER2) gene is amplified and/or over-expressed in about 20% of breast cancers. Two high-frequency, coding, non-synonymous Single Nucleotide Polymorphisms (SNPs) have been described in the HER2 gene. The first (Ile655Val) is related to a residue in the trans-membrane domain, the second (Ala1170Pro) induces an amino acid change in the intra-cellular carboxyl-terminal tail. We aimed to investigate the potential influence of these SNPs on the amplification/over-expression of HER2 in breast tumours. Methods: Breast cancer patients with known HER2 status in tumours were selected in an outpatient clinic. HER2 status (positive or negative) was assessed according to international standard criteria using Immuno-Histo-Chemistry and/or Fluorescent In Situ Hybridization. Germ-line DNA was extracted from peripheral nucleated blood cells and genotyping of the two SNPs was performed by fluorogenic 5' nuclease assay using the endogenous 5' nuclease activity of AmpliTaq Gold DNA polymerase. Results: Two hundred and ninety three patients were recruited in the study. Forty seven per cent of tumours were HER2-positive and 53% were HER2-negative. The genotypes were in Hardy-Weinberg equilibrium and minor allele frequency for Ile655Val and Ala1170Pro were respectively 21% and 29%. There was no correlation between Ile655Val genotype and HER2 status (proportions of HER2-positive tumours among Ile homozygous patients and carriers of the Val allele were respectively 46% and 48%, p=0.705). However, when the Ala1170Pro SNP was considered, the proportion of HER2-positive tumours was significantly higher among carriers of the Pro allele than it was among Ala homozygous patients (56% vs 38%, p=0.002). Conclusions: Our preliminary results suggest that the Ala1170Pro SNP in the HER2 gene may have a role in the development of HER2-positive breast tumours. Validation of this finding in a different population of patients, along with evaluation of allele-specific amplification in tumour samples is warranted.