ERCC2和MTHFR多态性与中国北方女性乳腺癌易感性间的相关性研究  

Study on the relationship between ERCC2 and MTHFR polymorphisms and the susceptibility of breast cancer in the female population of northern China

作　　者：丛佳 Cong Jia(Galactophore Department,Dalian Municipal Women and Children's Medical Center(Group),Dalian 116033)

机构地区：[1]大连市妇女儿童医疗中心(集团)乳腺科,辽宁大连116033

出　　处：《中国现代医药杂志》2021年第12期6-11,共6页Modern Medicine Journal of China

摘　　要：目的探究切除修复交叉互补组2(Resection repair cross complementation group 2,ERCC2)和亚甲基四氢叶酸还原酶(Methylenetetrahydrofolate reductase,MTHFR)多态性与中国北方女性乳腺癌易感性间的相关性。方法选取2018年9月~2020年3月我院乳腺科收治的165例女性乳腺癌患者为观察组,另选取同时间我院乳腺体检的健康女性165例作为对照组。回顾患者医疗档案,收集每例患者的相关临床病理特征。采集两组的静脉血2 ml,提取DNA,对ERCC2基因上rs1799793、rs13181和MTHFR基因上rs1801133、rs1801131的4个单核苷酸多态性(Single nucleotide polymorphism,SNP)位点采用TaqMan SNP基因分型的方法进行分型。采用哈迪温伯格平衡定律(Hardy-Weinberg equilibrium,HWE)分析两组ERCC2和MTHFR基因的多态性和等位基因分布;分析ERCC2位点单倍型和MTHFR位点单倍型发生乳腺癌的风险;分析ERCC2和MTHFR单倍型与乳腺癌患者临床年龄的关系及家族形成的风险。结果观察组ERCC2 rs1799793-rs1318单倍型A-C显著高于对照组,它与乳腺癌风险增加相关(OR=1.75,95%CI 1.39~2.54,P=0.016),而两组之间在其他基因型的分布上差异均无统计学意义(P>0.05);MTHFR rs1801133-rs1801131组成的单倍型两组之间差异均无统计学意义(P>0.05)。MTHFR rs1801133-rs1801131组成的单倍型T-C与≤40岁乳腺癌患者的发病风险相关联(OR=3.52,95%CI 1.25~10.39,P=0.047),其余各单倍型乳腺癌发病风险与年龄无关;MTHFR rs1801133-rs1801131组成的单倍型T-A和T-C与家族型乳腺癌的发病风险正相关联(OR=1.56和4.96,95%CI 0.95~3.72和0.47~7.62,P=0.009和0.033),MTHFR rs1801133-rs1801131组成的单倍型C-C与家族型乳腺癌的发病风险负相关联(OR=0.36,95%CI:0.14~0.95,P=0.001),而其余各单倍型乳腺癌的发病风险与家族形成无关。结论 ERCC2和MTHFR基因的多态性与中国北方女性乳腺癌的风险增加有关,同时MTHFR rs1801133-rs1801131组成的单倍型T-A和T-C与家族型乳腺癌相关,Objective To explore the relationship between resection repair cross complementation group 2(ERCC2) and methylenetetrahydrofolate reductase(MTHFR) polymorphisms and susceptibility of breast cancer in the female population of northern China. Methods 165 female breast cancer patients who were enrolled in our hospital from Sep 2018 to Mar 2020 were selected. 165 healthy women undergoing breast examinations at the same time in our hospital were selected as controls. By reviewing the patient’s medical files, the relevant clinicopathological characteristics of each case were collected. Collected 2 ml venous blood samples of two groups, DNA was extracted,and the four SNP sites of rs1799793, rs13181 on the ERCC2 gene and rs1801133, rs1801131 on the MTHFR gene were typed using TaqMan SNP genotyping method. Used Hardy-Weinberg equilibrium(HWE) to analyze the polymorphism and allele distribution of the two groups of ERCC2 and MTHFR genes;analyzed the haplotypes of ERCC2 locus and MTHFR locus and breast cancer risk;analyzed the risk of ERCC2 and MTHFR haplotypes and the clinical age of breast cancer patients and the risk of family formation. Results For ERCC2 rs1799793-rs1318, the haplotype A-C of the observation group was significantly higher than that of the control group, and it was associated with an increased risk of breast cancer(OR=1.75, 95%CI 1.39~2.54, P=0.016), while there were no significent difference between the two groups in the distribution of the other genestypes(P>0.05).No difference was observed between the two groups of haplotypes composed of MTHFR rs1801133-rs1801131(P>0.05). The haplotype T-C composed of MTHFR rs1801133-rs1801131 was associated with the risk of breast cancer patients age ≤40 years old(OR=3.52, 95%CI 1.25~10.39, P=0.047). The risk of cancer had no significant correlation with age in the other haplotypes. Haplotypes T-A and T-C composed of MTHFR rs1801133-rs1801131 were positively correlated with the risk of familial breast cancer(OR=1.56 and 4.96, 95%CI 0.95~3.72 and 0.47~7.62, P=0.00

关 键 词：乳腺癌 遗传多态性 单倍型 易感风险 ERCC2 MTHFR 

分 类 号：R737.9[医药卫生—肿瘤]