Format

Send to

Choose Destination
See comment in PubMed Commons below
Pharmacogenet Genomics. 2008 Mar;18(3):263-73. doi: 10.1097/FPC.0b013e3282f60a91.

Single nucleotide polymorphisms in the multidrug resistance gene 1 (ABCB1): effects on its expression and clinicopathological characteristics in breast cancer patients.

Author information

1
Biotransformation Group, Center of Occupational Health, National Institute of Public Health, Prague, Czech Republic. rvaclavikova@szu.cz

Abstract

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.

PMID:
18300948
DOI:
10.1097/FPC.0b013e3282f60a91
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Lippincott Williams & Wilkins
    Loading ...
    Support Center