title: Estrogen receptor alpha (ERS1) SNPs c454-397T>C (PvuII) and c454-351A>G (XbaI) are risk biomarkers for breast cancer development.
abstract: There are several risk factors related to Breast Cancer (BC) risks and response to chemotherapy with SERMs. Recently some single nucleotide polymorphisms (SNPs) on ESR1 gene have been associated to this disease. However, data are still inconclusive. The present study aimed to investigate the association of SNPs c454-397T>C (also called PvuII) and c454-351A>G (so called XbaI) to incidence of sporadic BC; ERα expression in BC; tamoxifen hormonetherapy (HT-TMX) responsiveness. To do so, a cohort of BC patients was analyzed through retrospective data collection, immunohistochemistry to ERα protein, and genotyping for PvuII and XbaI SNPs by PCR-RFLP, confirmed by sequencing. Significant difference in PvuII alleles frequencies were found BC patients when compared to control samples. Patients with P allele have a 5.14-fold increased BC risk. We found higher P and X alleles frequencies in ERα positive BC and the pp and xx genotypes were observed exclusively in patients with HT-TMX-responsive BC. Taken together, data indicates that P allele as a novel sporadic BC biomarker whereas p and x alleles enhanced chemotherapy responsiveness.
authors.affiliation: Biotechnology Program/RENORBIO, Health Sciences Center, Federal University of Espirito Santo, Vitoria, Brazil.
authors.forename: Klesia Pirola
authors.initials: KP
authors.lastname: Madeira
authors.forename: Renata Dalmaschio
authors.initials: RD
authors.lastname: Daltoé
authors.forename: Gabriela Modenesi
authors.initials: GM
authors.lastname: Sirtoli
authors.forename: Alex Assis
authors.initials: AA
authors.lastname: Carvalho
authors.forename: Leticia Batista Azevedo
authors.initials: LB
authors.lastname: Rangel
authors.forename: Ian Victor
authors.initials: IV
authors.lastname: Silva
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D005819:Genetic Markers; D013629:Tamoxifen