Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 9, December, p. 1425–1429

doi: 10.17219/acem/64877

Publication type: original article

Language: English

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Polymorphism of Gly39Glu (c.116G>A) hMSH6 is associated with sporadic colorectal cancer development in the Polish population: Preliminary results

Piotr Zelga1,A,B,C,D, Karolina Przybyłowska-Sygut2,A,C,E, Marta Zelga1,B,C, Adam Dziki1,A,E,F, Ireneusz Majsterek2,A,E,F

1 General and Colorectal Surgery Department, Medical University of Lodz, Poland

2 Department of Biochemistry, Medical University of Lodz, Poland

Abstract

Background. Colorectal cancer (CRC) remains a major source of cancer-related mortality, accounting for 10% of all cancer-related deaths. DNA mismatch repair mechanism (MMR) responsible for correcting errors generated during DNA replication and its deficiency is associated with both hereditary and sporadic CRC. Single-nucleotide polymorphisms (SNPs) are the most common forms of genetic variation, and it has been shown that the SNPs in MMR genes may modify CRC risk.
Objectives. The aim of the study was to determine the relationship between gene polymorphism Glu39Gly (c.116G>A) of the hMSH6 gene and the modulation of the risk of sporadic colorectal cancer in the Polish population.
Material and Methods. A total of 128 patients with resectable colorectal carcinoma as well as 189 sex-, age-, and ethnicity-matched control subjects without cancer history were enrolled in this study. Patients with a family history of CRC or inflammatory bowel diseases were excluded from this study. The DNA was isolated from peripheral blood lymphocytes of enrolled patients, and gene polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR).
Results. We observed that the genotype G/A variant of Glu39Gly (c.116G>A) genotype is associated with an increased risk of colorectal cancer (OR 1.65; 95% CI: 1.01–2.69; p = 0.44). The presence of A allele was also significantly higher in patients with CRC (OR 1.57; 95% CI: 1.04–2.38; p = 0.032). When comparing the prevalence of genotypes with clinical staging, genotype G/A and A allele were significantly less frequent in stage III–IV than in I (OR 0.3409; 95% CI: 0.124–0.939; p = 0.0375, and OR 0.4462; 95% CI: 0.201–0.991; p = 0.044, respectively).
Conclusion. These findings suggest that hMSH6 Glu39Gly polymorphism is associated with the risk of developing colorectal cancer in the Polish population, probably due to a defective mismatch repair system. The presence of G/A genotype and A allele is, however, associated with less advanced disease.

Key words

colorectal cancer, SNP, hMSH6, DNA MMR

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