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International Journal of Colorectal Disease

Published in:

01-08-2009 | Original Article

ABCB1 gene polymorphisms and haplotype analysis in colorectal cancer

Authors: Mariusz Panczyk, Ewa Balcerczak, Sylwester Piaskowski, Krzysztof Jamroziak, Grażyna Pasz-Walczak, Marek Mirowski

Published in: International Journal of Colorectal Disease | Issue 8/2009

Abstract

Purpose

The aim of this study was to determine the significance of three most common single-nucleotide polymorphisms (SNPs) of ABCB1 gene in the development of colorectal cancer and to estimate the influence of these SNPs to surviving patients' treatment combination adjuvant therapy 5-fluorouracil/leucovorin. Haplotype structure of ABCB1 was analysed, and degree of linkage disequilibrium (LD) between SNPs of ABCB1 was estimated.

Materials and methods

Tumour specimens of 95 patients with colorectal cancer and blood samples of 95 healthy cases were studied. Genotyping of ABCB1 gene was performed by automated sequencing or polymerase chain reaction-restriction fragment length polymorphism method. Comparison of frequencies of alleles/genotypes/haplotypes between the studied group (colorectal cancer samples) and the control group (blood samples) were analysed. These results were correlated with the surviving patients after treatment of adjuvant chemotherapy.

Results

Significant differences in ABCB1 _1236C>T (p = 0.00043) and ABCB1 _2677G>T/A (p = 0.04) genotype distribution and T₁₂₃₆ allele distribution (CT₁₂₃₆ or TT₁₂₃₆ vs CC₁₂₃₆; p = 0.0499, OR = 0.55, Fi–Yule coefficient = 0.14) were found. A strong LD between ABCB1 _1236C>T and ABCB1 _2677G>T/A SNPs (D′ = 0.621, r ² = 0.318) was detected. All SNPs were located in one haplotype block. There were significant differences in haplotype distributions between colorectal cancer patients and healthy population (p = 0.03). Significant differences in survival probability of colorectal cancer patients' treatment chemotherapy according to allele of ABCB1 _3435C>T was observed. Survival probability of patients with wild-type C₃₄₃₅ allele were higher than among patients without this allele (p = 0.04572).

Conclusions

These results suggested that three studied SNPs of ABCB1 were located in one haplotype block. Differences in ABCB1 _1236C>T and ABCB1 _2677G>T/A genotypes and T₁₂₃₆ allele distribution between investigated populations indicate significant impact of these SNPs on risk of development of colorectal cancer. Polymorphism ABCB1 _3435C>T may be a prediction marker of cancer chemotherapy effectiveness. Differences in haplotype distributions between colorectal cancer patients and healthy population suggested that other potential SNPs, especially in regulatory region of ABCB1 gene, may influence P-glycoprotein expression and function.

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Title: ABCB1 gene polymorphisms and haplotype analysis in colorectal cancer
Authors: Mariusz Panczyk
Ewa Balcerczak
Sylwester Piaskowski
Krzysztof Jamroziak
Grażyna Pasz-Walczak
Marek Mirowski
Publication date: 01-08-2009
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 8/2009
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-009-0724-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

ABCB1 gene polymorphisms and haplotype analysis in colorectal cancer

Abstract

Purpose

Materials and methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Materials and methods

Results

Conclusions

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