COX-2启动子基因多态性与结直肠癌相关性分析

  目的  探讨错配修复（MMR）基因MLH1 rs1800734、MSH2 rs3732183和代谢酶基因UGT1A1 rs3755319、GSTM3 rs7483、DPYD rs1801159单核苷酸多态性（SNP）与结直肠癌发病风险的关系，为结直肠癌的诊断和治疗提供分子水平的参考依据。  方法  整群抽取2016年1月 — 2017年7月在江苏省肿瘤医院住院治疗的690例结直肠癌患者作为病例组，选择同期在南京康爱医院进行体检的健康人群431人作为对照组，每人抽取2 mL外周静脉血，采用TaqMan实时荧光定量PCR方法进行基因分型，并应用χ²检验和多因素logistic回归模型进行MLH1 rs1800734、MSH2 rs3732183、UGT1A1 rs3755319、GSTM3 rs7483、DPYD rs1801159等5个多态性位点与结直肠癌的关系。  结果  病例组MLH1 rs1800734 AA + GA型和GG型基因型携带者分别占80.9 %和19.1 %，对照组分别占85.8 %和14.2 %；在校正性别和年龄后，MLH1 rs1800734隐性模型中GG基因型显著增加结直肠癌发病风险（OR = 1.440，95 % CI = 1.021～2.032，P = 0.038）。未发现MSH2 rs3732183、UGT1A1 rs3755319、GSTM3 rs7483和DPYD rs1801159与结直肠癌发病有相关性（均P > 0.05）。  结论  MLH1 rs1800734 SNP与结直肠癌的发病有关。

Polymorphisms in ATP-binding cassette transporter genes and interaction with diet and life style factors in relation to colorectal cancer in a Danish prospective case-cohort study

  Objective  To explore the relationship between single nucleotide polymorphisms (SNP) of mismatch repair gene (MMR) MLH1 rs1800734, MSH2 rs3732183 and metabolic enzyme gene UGT1A1 rs3755319, GSTM3 rs7483, DPYD rs1801159 and the risk of colorectal cancer for providing a molecular basis for diagnosis and treatment of colorectal cancer.  Methods  We recruited 690 colorectal cancer patients hospitalized in Jiangsu Province Cancer Hospital during 2016 – 2017 as the cases and 431 healthy people having physical examination in Nanjing Kang′ai Hospital during the same period as the controls. Peripheral venous blood samples (2 mL for each participant) were collected for genotyping of relevant genes with TaqMan real-time PCR. The relationship between SNPs of the 5 gene loci and risk of colorectal cancer was analyzed using χ² test and logistic regression.  Results  The ratios of MLH1 rs1800734 AA + GA and GG genotype carriers were 80.9% and 19.1% in the cases and the ratios were 85.8% and 14.2% in the controls. After adjusting for gender and age, GG genotype of MLH1 rs1800734 in recessive model was significantly associated with increased risk of colorectal cancer (odds ratio = 1.440, 95% confidence interval: 1.021 – 2.032; P = 0.038). No significant correlations were observed between SNPs of MSH2 rs3732183, UGT1A1 rs3755319, GSTM3 rs7483 and DPYD rs1801159 and colorectal cancer (both P > 0.05).  Conclusion  The SNP of MLH1 rs1800734 is associated with the risk of colorectal cancer.