Zelga Piotr, Przybyłowska-Sygut Karolina, Zelga Marta, Dziki Adam, Majsterek Ireneusz
General and Colorectal Surgery Department, Medical University of Lodz, Poland.
Department of Biochemistry, Medical University of Lodz, Poland.
Adv Clin Exp Med. 2017 Dec;26(9):1425-1429. doi: 10.17219/acem/64877.
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.
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.
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).
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).
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.
结直肠癌（CRC）仍是癌症相关死亡的主要原因，占所有癌症相关死亡的10%。负责纠正DNA复制过程中产生错误的DNA错配修复机制（MMR）及其缺陷与遗传性和散发性CRC均有关联。单核苷酸多态性（SNP）是最常见的基因变异形式，并且已经表明MMR基因中的SNP可能会改变CRC风险。
本研究的目的是确定hMSH6基因的Glu39Gly（c.116G>A）基因多态性与波兰人群散发性结直肠癌风险调节之间的关系。
本研究共纳入128例可切除的结直肠癌患者以及189例无癌症病史、性别、年龄和种族匹配的对照受试者。有CRC家族史或炎症性肠病的患者被排除在本研究之外。从纳入患者的外周血淋巴细胞中分离DNA，并通过限制性片段长度多态性-聚合酶链反应（RFLP-PCR）分析基因多态性。
我们观察到Glu39Gly（c.116G>A）基因型的G/A变异与结直肠癌风险增加相关（OR 1.65；95%CI：1.01-2.69；p = 0.44）。CRC患者中A等位基因的存在也显著更高（OR 1.57；95%CI：1.04-2.38；p = 0.032）。当比较不同临床分期的基因型患病率时，III-IV期的G/A基因型和A等位基因频率显著低于I期（分别为OR 0.3409；95%CI：0.124-0.939；p = 0.0375，以及OR 0.4462；95%CI：0.201-0.991；p = 0.044）。
这些发现表明，hMSH6 Glu39Gly多态性与波兰人群患结直肠癌的风险相关，可能是由于错配修复系统存在缺陷。然而，G/A基因型和A等位基因的存在与疾病进展程度较低有关。
