结直肠癌KRAS、NRAS和BRAF 基因突变与病理特征、吸烟和饮酒之间的相关性
Relationship between KRAS,NRAS and BRAF gene mutation and pathological features,smoking and drinking of patients with colorectal cancer

目的：探讨 KRAS、NRAS和BRAF基因在结直肠癌中的突变率，分析3种基因突变与结直肠癌病理特征、吸烟和饮酒之间的关系。方法：用石蜡组织DNA提取试剂盒提取DNA，应用实时荧光定量PCR技术检测结直肠癌组织中KRAS 2号外显子的12密码子和13密码子常见的7个突变位点，检测NRAS 2号与3号外显子的12密码子、13密码子与61密码子常见的12个突变位点，检测BRAF 15号外显子的V600E位点的突变，分析KRAS、NRAS和 BRAF 基因在结直肠癌中的突变率与病理特征、吸烟和饮酒之间的相关性。结果：KRAS、NRAS和BRAF基因的突变率分别为38.0%（93/242）、5.0%（12/237）和2.1%（5/237）。在147例KRAS 野生型病例中NRAS与BRAF的突变频率为6.8%（10/147）和3.4%（5/147）。BRAF与KRAS、NRAS基因突变相互排斥。KRAS基因突变更倾向发生于Duke′S分期的C期（P=0.047）和淋巴结转移的患者（P=0.049），与年龄、性别、肿瘤部位、组织学类型、分化程度、远处转移、癌结节及AJCC分期等病理特征无关（P均>0.05）。NRAS和BRAF基因突变与病理特征无关（P均>0.05）。KRAS、NRAS和BRAF 基因突变与吸烟及饮酒史无关（P>0.05）。结论：该研究中KRAS基因突变更倾向发生淋巴结转移和Duke′S C期，说明KRAS基因突变对转移性结直肠癌有更重要的临床意义。
Aim: To discuss KRAS, NRAS and BRAF gene mutation rates in colorectal cancer and to analyze the rela？？tionship between KRAS, NRAS and BRAF gene mutation and the pathological features smoking and drinking of patients with colorectal cancer.Methods: DNA was extracted with paraffin tissue DNA extraction kit, real？？time fluorescent quantitative PCR technology was used to detect 7 mutations in codons 12, 13 of exon 2 of KRAS,12 mutations in codons 12, 13 and 61 of exon 2, 3 of NRAS, and BRAF mutation in V600E of exon 15 in colorectal cancer tissue, and to analyze the relationship between KRAS, NRAS and BRAF gene mutation and pathological features, smoking, and drinking in patients with colorectal cancer.Results: KRAS, NRAS and BRAF gene mutation rate was 38.0%(93/242), 5.0%(12/237), 2.1%(5/237), respectively. Among 147 patients with wild？？type KRAS, the mutation rate of NRAS was 6.8%(10/147), and BRAF was 3.4% (5/147). BRAF, KRAS and NRAS mutation was mutually exclusive. KRAS mutation was more likely occurred in the Duke′S stage C patients(P=0.047) and lymph node metastasis patients(P=0.049),and there was no significant relation between KRAS mutation and age, gender, tumor location, histological type, differentiation degree, distant metastasis, nodules, or AJCC staging(P>0.05). And there was no significant relation between NRAS and BRAF gene mutation and pathological features(P>0.05). KRAS, NRAS and BRAF gene mutation was not obviously associated with a history of smoking or drinking(P>0.05).Conclusion: In this study,the KRAS gene more likely occurs in patients with lymph node metastasis and Duke′S C period, indicating that KRAS gene mutation has more important clinical significance for metastatic colorectal cancer