title: Single nucleotide polymorphisms in the multidrug resistance gene 1 (ABCB1): effects on its expression and clinicopathological characteristics in breast cancer patients.
abstract: OBJECTIVE
  Resistance of tumor cells to multiple cytostatic agents is one of the major impediments of successful cancer chemotherapy. A large part of resistance of tumors to chemotherapy is caused by the ABC transporter P-glycoprotein encoded by the ABCB1 gene. The main aim of this study was to assess the prognostic value of ABCB1 genotype and phenotype in breast cancer.
  
  
  METHODS
  Six ABCB1 single nucleotide polymorphisms (SNPs) were determined in 90 Czech breast cancer patients by a novel method that allows simultaneous assessment of multiple polymorphisms on a single electronic microarray. Expression levels of ABCB1 were quantified in tumor and nontumor samples of breast cancer patients by real-time PCR. T-test, analysis of variance and Fisher's exact test were used to analyze the effect of ABCB1 polymorphisms on ABCB1 expression levels and for the analysis of associations between ABCB1 expression, genotype and clinical and pathological characteristics.
  
  
  RESULTS
  ABCB1 was expressed in 98.9% of the tumor and in 97.5% of the nontumor samples. ABCB1 was downregulated in 79.5% of tumors compared with the nontumor samples. No significant correlation was observed between ABCB1 mRNA expression levels and clinical and pathological characteristics. High frequencies of the variant alleles in ABCB1 exon 12 (1236C>T, 38.3%) and exon 26 (3435C>T, 54.0%) were observed. Individuals with variant alleles in exons 12 and 26 had significantly lower ABCB1 expression levels in their tumors. SNPs in exons 12 and 26 also correlated with estrogen receptor status of patients.
  
  
  CONCLUSIONS
  ABCB1 SNPs may affect function of P-glycoprotein by influencing the expression level and modify breast cancer prognosis.
authors.affiliation: Biotransformation Group, Center of Occupational Health, National Institute of Public Health, Prague, Czech Republic. rvaclavikova@szu.cz
authors.forename: Radka
authors.initials: R
authors.lastname: Vaclavikova
authors.forename: Silje H
authors.initials: SH
authors.lastname: Nordgard
authors.forename: Grethe I G
authors.initials: GI
authors.lastname: Alnaes
authors.forename: Miluse
authors.initials: M
authors.lastname: Hubackova
authors.forename: Eugen
authors.initials: E
authors.lastname: Kubala
authors.forename: Roman
authors.initials: R
authors.lastname: Kodet
authors.forename: Marcela
authors.initials: M
authors.lastname: Mrhalova
authors.forename: Jan
authors.initials: J
authors.lastname: Novotny
authors.forename: Ivan
authors.initials: I
authors.lastname: Gut
authors.forename: Vessela N
authors.initials: VN
authors.lastname: Kristensen
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D017931:DNA Primers / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen