Estrogen receptor-α polymorphism in a Taiwanese clinical breast cancer population: A case-control study

Introduction: Receptor-mediated estrogen activation participates in the development and progression of breast cancer. Estrogen receptor (ER)-α polymorphism has been found to be associated with breast cancer and clinical features of the disease in Caucasians. Epidemiologic studies have revealed that age-incidence patterns of breast cancer in Asians differ from those in Caucasians. Genomic data for ER-α in either population is therefore of value in the clinical setting for that ethnic group. Methods: A case-control study was conducted to establish a database of ER-α polymorphisms in a Taiwanese population in order to compare Western and Taiwanese (Asian) distributions and to evaluate ER-α polymorphism as an indicator of clinical outcome. The ER-α gene was scanned in a Taiwanese clinical breast cancer group (189 patients) and in healthy individuals (177 healthy control individuals). PCR single-strand conformation polymorphism technology was employed and real-time PCR melting curve analysis was performed. Results: Three sites of silent single nucleotide polymorphism (SNPs) were found, as reported previously in Western studies, but at significantly different frequencies. Among the three SNPs, the frequency of allele 1 (TCTTCC) in codon 10 was significantly lower in breast cancer patients (32.0%) than in control individuals (40.4%; P = 0.018). We found that allele 1 (ACGACA) in codon 594 was less common in breast cancer patients with a family history of breast cancer (5.9%) than in those without such a history (19.6%; P = 0.049). Individually, both allele 1 in codon 325 (CCCCCG) and allele 1 in codon 594 exhibited a reverse association with the occurrence of lymph node metastasis. Furthermore, incorporation of both SNP markers further increased predictive accuracy. Conclusions: Our data suggest that ER-α polymorphisms are correlated with various aspects of breast cancer in Taiwan. ER-α genotype, as determined during presurgical evaluation, might represent a surrogate marker for predicting breast cancer lymph node metastasis.