Servicio de Cardiología, Hospital Clínico Universitario, Valladolid, Spain.
Colorectal Dis. 2013 Mar;15(3):e118-23. doi: 10.1111/codi.12112.
The MLH1 promoter contains a common single nucleotide polymorphism (-93 guanine > adenine) located in an essential region for maximum transcriptional activity. This has been associated with an increased risk of microsatellite instability (MSI) colorectal cancer. The aim of the study was to compare the distribution of MLH1 -93G>A genotypes between patients with familial colon cancer, sporadic colon cancer and healthy subjects.
We genotyped 200 familial colon samples, 183 cases of sporadic colon cancer and 236 control subjects. MSI was analysed.
The GA genotype was under-represented in patients with familial colon cancer, whereas the AA genotype was over-represented in cases of sporadic colon cancer. A greater frequency of the MLH1 GA genotype was found in the cancer cases with MLH1 focal immunohistochemistry (IHC) for anti-MLH1 antibody. When we compared genotype distribution in the familial colorectal cancer cases with and without MSI, we failed to detect any correlation, although the GA genotype is more frequent in cases with MSI.
There is a relationship between the MLH1 -93G>A polymorphism in the homozygous state and the risk of sporadic colorectal cancer. The variant MLH1 -93G>A appears to be related to cases with focal IHC activity more than to complete absence of the MLH1 protein in the tumour tissue.
MLH1 启动子含有一个常见的单核苷酸多态性（-93 位鸟嘌呤>腺嘌呤），位于最大转录活性的必需区域。这与微卫星不稳定性（MSI）结直肠癌的风险增加有关。本研究旨在比较家族性结肠癌、散发性结肠癌患者和健康受试者之间 MLH1-93G>A 基因型的分布。
我们对 200 例家族性结肠癌样本、183 例散发性结肠癌病例和 236 例对照进行了基因分型。分析了 MSI。
GA 基因型在家族性结肠癌患者中表达不足，而 AA 基因型在散发性结肠癌病例中表达过度。在 MLH1 焦点免疫组化（IHC）抗 MLH1 抗体的癌症病例中，发现 MLH1GA 基因型的频率更高。当我们比较有和没有 MSI 的家族性结直肠癌病例的基因型分布时，虽然 GA 基因型在 MSI 病例中更为常见，但未发现任何相关性。
MLH1-93G>A 多态性在纯合状态下与散发性结直肠癌的风险之间存在关联。变异 MLH1-93G>A 似乎与肿瘤组织中 MLH1 蛋白的焦点 IHC 活性有关，而不是与完全缺失有关。
