ABCB1-MDR1 gene polymorphisms as a prognostic factor in colorectal cancerReport as inadecuate




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International Journal of Colorectal Disease

, Volume 25, Issue 10, pp 1167–1176

First Online: 09 June 2010Accepted: 21 May 2010

Abstract

ObjectiveTo analyse the single-nucleotide polymorphisms SNPs: ABCB11236C>T, ABCB12677G>T-A, ABCB13435C>T and haplotypes in the ABCB1-MDR1 gene, which could contribute to genetic risk of colorectal cancer CRC. Disease association between the ABCB1-MDR1 genotype, allele, haplotype frequencies and histological features, such as TNM classification, localization of primary carcinoma, grade of malignancy, histological type of tumour, lymphoid infiltration and vessel invasion were estimated. In this study, the potential role of SNPs of the ABCB1-MDR1 gene as a prognostic marker for CRC was analysed.

Materials and methodsTumour specimens of 95 patients with CRC were studied. Using automated sequencing or PCR-RFLP method, DNA for three common SNPs of ABCB1-MDR1 was extracted and analysed. The results of genotyping and haplotype analysis with histopathological features, grading and clinical staging of neoplasms were correlated.

ResultsA statistically significant higher frequency of T1236 allele in T1-T2 89.7%, M0 groups 81.6% and I-II clinical staging 82.7% in comparison with T3-T4 68.2%, M1 groups 47.4% and III-IV clinical staging 65.1% was detected. Furthermore, multivariate analysis according to Cox-s proportional hazard model indicated that the T1236 allele is a good, independent prognostic factor and the presence of this allele decreases the risk of death in comparison with a group without this allele HR = 0.26; p = 0.0424. In addition, a statistically significant higher frequency of C3435 allele and significant differences in the C3435 allele distribution in N1-N2 group 91.7% and 62.5%, respectively than N0 group 71.2% and 44.9%, respectively was found. Each of the eight possible haplotypes was noted in M0 or I-II group and only seven in M1 or III-IV group. Haplotype T1236-G2677-C3435 only in less advanced CRC subjects 9.6% in I-II and 9.2% in M0 group was detected. In addition, significant differences in haplotype distributions between M0 or I-II and M1 or III-IV group were found p = 0.01 and p = 0.05, respectively.

ConclusionsThese results suggest association between T1236 allele and T1236-G2677-C3435 haplotype and less advanced CRC, so these genetic markers may play a role as potentially good prognostic factors. Differences in haplotype distributions and degree of clinical staging may suggest that some other potential SNPs, especially in regulatory region of ABCB1-MDR1 gene, may influence P-glycoprotein function and CRC progression.

KeywordsABCB1 gene MDR1 gene Polymorphism Haplotype analysis Colorectal cancer  Download fulltext PDF



Author: Ewa Balcerczak - Mariusz Panczyk - Sylwester Piaskowski - Grażyna Pasz-Walczak - Aleksandra Sałagacka - Marek Mirowski

Source: https://link.springer.com/article/10.1007/s00384-010-0961-2







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