Poplawski T, Sobczuk A, Sarnik J, Pawlowska E, Blasiak J
Department of Molecular Genetics, University of Lodz, Lodz 90-236, Poland.
Department of Gynaecology and Obstetrics, Medical University of Lodz, Lodz 94-029, Poland.
Exp Oncol. 2015 Mar;37(1):44-7.
Endometrial cancer (EC) is the second most common malignancy associated with hereditary non-polyposis colorectal cancer (HNPCC) family. The development of HNPCC is associated with defects in DNA mismatch repair (MMR) pathway resulting in microsatellite instability (MSI). MSI is present in a greater number of EC than can be accounted for by inherited MMR mutations, therefore alternative mechanisms may underline defective MMR in EC, including polymorphic variation.
We checked the association between EC occurrence and two polymorphisms of MMR genes: a 1032G>A (rs4987188) transition in the hMSH2 gene resulting in a Gly22Asp substitution and a -93G>A (rs1800734) transition in the promoter of the hMLH1 gene.
These polymorphisms were genotyped in DNA from peripheral blood lymphocytes of 100 EC patients and 100 age-matched women by restriction fragment length polymorphism PCR.
A positive association (OR 4.18; 95% CI 2.23-7.84) was found for the G/A genotype of the -93G>A polymorphism of the hMLH1 gene and EC occurrence. On the ot-her hand, the A allele of this polymorphism was associated with decreased EC occurrence. The Gly/Gly genotype slightly increased the effect of the -93G>A-G/A genotype (OR 4.52; CI 2.41-8.49). Our results suggest that the -93G>A polymorphism of the hMLH1 gene singly and in combination with the Gly322Asp polymorphism of the hMSH2 gene may increase the risk of EC.
子宫内膜癌（EC）是与遗传性非息肉病性结直肠癌（HNPCC）家族相关的第二常见恶性肿瘤。HNPCC的发生与DNA错配修复（MMR）途径缺陷有关，导致微卫星不稳定性（MSI）。EC中存在MSI的数量比遗传性MMR突变所能解释的更多，因此替代机制可能是EC中MMR缺陷的基础，包括多态性变异。
我们检查了EC发生与MMR基因的两种多态性之间的关联：hMSH2基因中导致Gly22Asp替代的1032G>A（rs4987188）转换以及hMLH1基因启动子中的-93G>A（rs1800734）转换。
通过限制性片段长度多态性PCR对100例EC患者和100例年龄匹配女性外周血淋巴细胞DNA中的这些多态性进行基因分型。
发现hMLH1基因-93G>A多态性的G/A基因型与EC发生呈正相关（OR 4.18；95%CI 2.23 - 7.84）。另一方面，该多态性的A等位基因与EC发生率降低相关。Gly/Gly基因型略微增加了-93G>A - G/A基因型的效应（OR 4.52；CI 2.41 - 8.49）。我们的结果表明，hMLH1基因的-93G>A多态性单独以及与hMSH2基因的Gly322Asp多态性联合可能增加EC风险。
