Fan Yimei, Liu Xiaorong, Zhang Huan, Dai Jin, Zhang Xiaomei, Zhu Ming, Gao Xiang, Wang Yaping
Department of Medical Genetics, Medical School, Nanjing University, Nanjing, China.
Cancer Genet Cytogenet. 2006 Oct 15;170(2):121-8. doi: 10.1016/j.cancergencyto.2006.05.010.
Epidemiologic, structural, and bioinformatic analyses were used to evaluate variants in the MSH2 and MLH1 genes in 187 subjects with suspected hereditary gastrointestinal cancer in China. An increased frequency of variants was observed in exon 7 of the MSH2 gene; there was a statistical difference (P < 0.05) between the colorectal cancer (CRC) group (6/82, or 7.32%) or the gastric cancer (GC) group (8/105, or 7.62%) and the controls (1/112, or 0.89%). The odds ratio (OR) was 8.76 for CRC and 9.15 for GC, suggesting an association between the presence of variants in exon 7 of the MSH2 gene and risk of gastrointestinal cancer in the studied population. In addition, MSH2 1168T showed trends toward association with CRC and GC in young (<50 yr) sporadic disease patients (OR = 10.97 and 17.15, respectively). The c.1168C>T (p.Leu390Phe), c.1255C>A (p.Gln419Lys), and c.1261C>A (p.Leu421Met) in exon 7 and c.518T>G (p.Leu173Arg) in exon 3 of MSH2 were suspected as predisposing to gastrointestinal cancer. Variants c.505A>G (p.Ile169Val), c.1221C>G (p.Leu407Leu) and c.1223A>G (p.Tyr408Cys) in MSH2 and c.655 A>G (p.Ile219 Val) and c.927C>T (p.Pro309Pro) in MLH1 might be merely polymorphisms. Consequences of the variant c.2101C>A (p.Gln701Lys) in MLH1 remain to be elucidated.
采用流行病学、结构和生物信息学分析方法，对187例中国疑似遗传性胃肠道癌患者的MSH2和MLH1基因变异进行评估。在MSH2基因第7外显子中观察到变异频率增加；结直肠癌（CRC）组（6/82，即7.32%）或胃癌（GC）组（8/105，即7.62%）与对照组（1/112，即0.89%）之间存在统计学差异（P<0.05）。CRC的优势比（OR）为8.76，GC为9.15，提示MSH2基因第7外显子变异的存在与所研究人群的胃肠道癌风险之间存在关联。此外，MSH2 1168T在年轻（<50岁）散发性疾病患者中显示出与CRC和GC相关的趋势（OR分别为10.97和17.15）。MSH2基因第7外显子中的c.1168C>T（p.Leu390Phe）、c.1255C>A（p.Gln419Lys）和c.1261C>A（p.Leu421Met）以及第3外显子中的c.518T>G（p.Leu173Arg）被怀疑易患胃肠道癌。MSH2中的变异c.505A>G（p.Ile169Val）、c.1221C>G（p.Leu407Leu）和c.1223A>G（p.Tyr408Cys）以及MLH1中的c.655 A>G（p.Ile219 Val）和c.927C>T（p.Pro309Pro）可能仅仅是多态性。MLH1中变异c.2101C>A（p.Gln701Lys）的后果仍有待阐明。
