Single nucleotide polymorphisms in the multidrug resistance gene 1 (ABCB1): effects on its expression and clinicopathological characteristics in breast cancer patients
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
18300948
DOI
10.1097/fpc.0b013e3282f60a91
PII: 01213011-200803000-00011
Knihovny.cz E-zdroje
- MeSH
- alely MeSH
- chemorezistence genetika MeSH
- DNA primery genetika MeSH
- dospělí MeSH
- farmakogenetika MeSH
- frekvence genu MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- mnohočetná léková rezistence genetika MeSH
- nádory prsu farmakoterapie genetika metabolismus patologie MeSH
- P-glykoprotein genetika MeSH
- P-glykoproteiny MeSH
- polymerázová řetězová reakce MeSH
- prognóza MeSH
- receptory pro estrogeny metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- RNA nádorová genetika MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABCB1 protein, human MeSH Prohlížeč
- DNA primery MeSH
- messenger RNA MeSH
- P-glykoprotein MeSH
- P-glykoproteiny MeSH
- receptory pro estrogeny MeSH
- RNA nádorová MeSH
OBJECTIVES: 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. CONCLUSION: ABCB1 SNPs may affect function of P-glycoprotein by influencing the expression level and modify breast cancer prognosis.
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