微卫星不稳定性（MSI）已被认为是结直肠癌（CRC）的重要因素。它是由于错配修复 (MMR) 缺陷引起的，主要归因于 MLH1 和 MSH2 功能丧失，导致影响单核苷酸和较长微卫星位点的整体 MMR 缺陷。最近，四核苷酸位点的微卫星不稳定性，与整体 MMR 缺陷背景无关，被认为代表了一个独特的实体，可能对肿瘤发生产生不同的后果。它是由于孤立的 MSH3 在白细胞介素 6 (IL-6) 的影响下从细胞核易位到细胞质而丧失功能的结果。本研究探讨了 MSH3 和 IL-6 信号通路多态性（MSH3 外显子 1、MSH3 3133A/G、IL-6-174G/C、IL-6R 48892A/C 和 gp130 148G/C）对不同疾病发生的影响。通过 PCR-RFLP 和实时 PCR SNP 分析检查散发性 CRC 中微卫星不稳定性的类型。在 CRC 患者中观察到 gp130 148G/C 基因型 (p = 0.037) 和等位基因 (p = 0.031) 分布存在显着差异，其中 C 等位基因在二核苷酸和四核苷酸不稳定的肿瘤中不太常见（孤立的 MSH3 功能丧失）与没有微卫星不稳定性的肿瘤相比。 gp130 的功能多态性可能会调节 IL-6 信号通路，引导其发生与 IL-6 介导的 MSH3 功能丧失相对应的微卫星不稳定性。

Microsatellite instability (MSI) has been recognized as an important factor in colorectal cancer (CRC). It arises due to deficient mismatch repair (MMR), mostly attributed to MLH1 and MSH2 loss of function leading to a global MMR defect affecting mononucleotide and longer microsatellite loci. Recently, microsatellite instability at tetranucleotide loci, independent of the global MMR defect context, has been suggested to represent a distinct entity with possibly different consequences for tumorigenesis. It arises as a result of an isolated MSH3 loss of function due to its translocation from the nucleus to the cytoplasm under the influence of interleukin-6 (IL-6). In this study the influence of MSH3 and IL-6 signaling pathway polymorphisms (MSH3 exon 1, MSH3+3133A/G, IL-6-174G/C, IL-6R+48892A/C, and gp130+148G/C) on the occurrence of different types of microsatellite instability in sporadic CRC was examined by PCR-RFLP and real-time PCR SNP analyses. A significant difference in distribution of gp130+148G/C genotypes (p = 0.037) and alleles (p = 0.031) was observed in CRC patients with the C allele being less common in tumors with di- and tetranucleotide instability (isolated MSH3 loss of function) compared to tumors without microsatellite instability. A functional polymorphism in gp130 might modulate the IL-6 signaling pathway, directing it toward the occurrence of microsatellite instability corresponding to the IL-6-mediated MSH3 loss of function.