MLH1基因415G／C多态与结肠癌遗传易感性的关联研究

Association of MLH1 gene 415G/C polymorphism with colorectal cancer in Chinese

目的探讨MLH1基因415G／C多态与我国汉族人群结肠癌发生的关系。方法收集97例散发结肠癌患者，138名正常对照，以及5个结肠癌家系的6例结肠癌患者，19名直系亲属。采用聚合酶链反应-限制性片段长度多态性分析法检测外周血MLH1基因415位点多态性。采用逆转录-聚合酶链反应检测各基因型结肠癌患者正常结肠黏膜的MLH1mRNA表达。结果散发结肠癌患者MLH1基因415位点CC基因型频率明显高于正常对照（P=0．035，OR=5．29，95％CI：1．07～26．04）。结肠癌家系中患者和直系亲属的C等位基因的频率明显高于散发患者和正常对照（P=0．003和P=0．006）。各基因型结肠癌患者正常结肠黏膜的MLH1mRNA表达差异无统计学意义。结论MLH1基因415G／C多态可能是我国散发结肠癌的遗传易感因素，但不是通过下调MLH1mRNA表达而致病的。结肠癌家系中C等位基因携带者患结肠癌可能性更大。

Objective To study the possible etiological role of MLH1 gene 415G/C polymorphism in sporadic Chinese colorectal cancer （CRC） patients. Methods Ninety seven sporadic CRC patients and 138 normal controls were collected from Hubei Provincial Cancer Hospital and the People＇s Hospital of Wuhan University. In addition, five CRC families including 6 patients and their 19 first-degree relatives were also recruited. Genomic DNA was extracted from peripheral blood samples. Gene mutation was analyzed by PCR-RFLP. MLH1 mRNA expression in eolorectal mucosa was analyzed by RT-PCR. Results The frequency of MLH1 gene CC genotype was significantly higher in sporadic CRC patients than that in controls （P=0. 035, OR=5.29, 95%CI： 1.07-26.04）. In the CRC families, the C allele frequency of CRC patients and their relatives was increased, compared with sporadic CRC patients and normal controls, respectively （P =0. 003 and P=0. 006）. MLH1 mRNA expression of colorectal mucosa was similar in different genotypes. Conclusion MLH1 gene 415G/C polymorphism might be a risk factor to sporadic CRC in Chinese. The mutation does not affect the MLH1 mRNA expression. For first-degree relatives from CRC families, carriers of MLH1 415C allele have a high risk to CRC.