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 T(1236) allele distribution (CT(1236) or TT(1236) vs CC(1236); 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 C(3435) 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 T(1236) 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.