Single nucleotide polymorphisms in the multidrug resistance gene 1 (ABCB1): effects on its expression and clinicopathological characteristics in breast cancer patients
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18300948
DOI
10.1097/fpc.0b013e3282f60a91
PII: 01213011-200803000-00011
Knihovny.cz E-resources
- MeSH
- Alleles MeSH
- Drug Resistance, Neoplasm genetics MeSH
- DNA Primers genetics MeSH
- Adult MeSH
- Pharmacogenetics MeSH
- Gene Frequency MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Messenger genetics MeSH
- Drug Resistance, Multiple genetics MeSH
- Breast Neoplasms drug therapy genetics metabolism pathology MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics MeSH
- ATP Binding Cassette Transporter, Subfamily B MeSH
- Polymerase Chain Reaction MeSH
- Prognosis MeSH
- Receptors, Estrogen metabolism MeSH
- Gene Expression Regulation, Neoplastic MeSH
- RNA, Neoplasm genetics MeSH
- Base Sequence MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ABCB1 protein, human MeSH Browser
- DNA Primers MeSH
- RNA, Messenger MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 MeSH
- ATP Binding Cassette Transporter, Subfamily B MeSH
- Receptors, Estrogen MeSH
- RNA, Neoplasm 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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