三阴性乳腺癌COMT、APOE和BDNF基因多态性与其化疗后认知功能障碍的相关性研究

发布时间：2018-05-24 23:16

  本文选题：COMT + 多态性　； 参考：《安徽医科大学》2017年硕士论文

【摘要】：背景:不同分子分型的乳腺癌具有不同的治疗及预后,化疗是乳腺癌治疗的重要手段之一,现有的研究证据表明乳腺癌化疗后存在不同程度的认知功能障碍,而COMT、APOE和BDNF基因的不同表达与认知功能密切相关。乳腺癌化疗后认知功能障碍的发生是否与其COMT、APOE和BDNF基因多态性有关,目前尚不清楚。目的:探讨三阴性乳腺癌COMT、APOE和BDNF基因多态性与其化疗后认知功能障碍发生的相关性。方法:分别对80例三阴性和165例年龄、教育程度相匹配的非三阴性乳腺癌患者化疗前后进行认知神经性心理学量表测查,包括前瞻性记忆(Prospective memory,PM)和回顾性记忆(Retrospective memory,RM)问卷调查。对入组对象进行COMT(rs165599,rs4680,rs737865),APOE(rs429358,rs7412)和BDNF(rs6265)6个单核苷多态性(SNP)位点的基因检测,同时分析各个基因位点和化疗后认知功能障碍的相关性。结果:1)乳腺癌患者化疗前后总体认知功能MMSE(27.26±1.58 vs.26.76±1.62)、DST(6.19±0.73 vs.5.78±0.97)、VFT(11.46±1.52 vs.9.99±2.11),差异具有的统计学意义(z=-2.942,z=-4.62,z=-7.87;p0.01);乳腺癌患者化疗前后RM问卷调查(16.23±4.03 vs.17.21±4.59)和PM问卷调查(16.01±4.64 vs.18.20±4.51),差异具有统计学意义(z=-3.37,t=-5.32;p0.01);2)与非三阴性乳腺癌患者相比,三阴性乳腺癌患者化疗后在MMSE(26.20±1.67 vs.27.03±1.52)、DST(5.29±1.01 vs.6.02±0.86)、VFT(8.40±1.65 vs.10.76±1.87)得分上均明显低于非三阴性乳腺癌,差异具有的统计学意义(z=-3.74,t=-5.88,t=-9.64;p0.01)。三阴性乳腺癌患者化疗后RM问卷调查(19.10±2.36),明显高于非三阴组(16.29±5.10),差异具有统计学意义(z=-5.33;p0.01);三阴性乳腺癌患者PM问卷调查(20.44±3.41),明显高于非三阴组(17.12±4.58),差异具有统计学意义(z=-5.99;p0.01)。3)所检测的6个SNP位点中,乳腺癌患者COMT(rs165599)位点上G/A基因型(校正,OR=0.515,95%CI=0.272-0.977,p=0.048)和A/A基因型(校正,OR=0.318,95%CI=0.136-0.742,p=0.048)较G/G基因型显著降低认知功能损害发生的几率。而两组乳腺癌患者上的APOE(rs429358,rs7412)及BDNF(rs6265)均未发现统计学差异。4)进一步分析COMT(rs165599)位点和化疗后认知功能障碍的相关性,发现显性模型(dominant model,β=-1.441,95%CI=-2.781~-0.101)与回顾性记忆成绩显著相关。结论:三阴性乳腺癌化疗后认知功能障碍较非三阴乳腺癌患者重,并且COMT(rs165599)位点与RM成绩呈线性相关,提示三阴性乳腺癌患者COMT基因多态性可能是化疗后认知功能障碍的遗传学易感因子。
[Abstract]:Background: different molecular types of breast cancer have different treatment and prognosis. Chemotherapy is one of the important methods of breast cancer treatment. The existing research evidence shows that breast cancer has different degree of cognitive dysfunction after chemotherapy. The different expression of COMTA APOE and BDNF genes is closely related to cognitive function. It is not clear whether the occurrence of cognitive dysfunction after chemotherapy in breast cancer is related to the polymorphism of COMTA APOE and BDNF genes. Objective: to investigate the association of COMTA APOE and BDNF gene polymorphisms with cognitive dysfunction after chemotherapy in triple negative breast cancer. Methods: a total of 80 patients with three-negative breast cancer and 165 patients with non-triple-negative breast cancer with matched age and education were investigated by cognitive neuropsychological scale before and after chemotherapy, including prospective memory PMMand retrospective memory RMs. The genes of 6 mononucleoside polymorphism loci (COMTR rs165599 rs4680 rs737865) and BDNFR rs6265) were detected, and the correlation between each locus and cognitive dysfunction after chemotherapy was analyzed. 缁撴灉:1)涔宠吅鐧屾偅鑰呭寲鐤楀墠鍚庢，

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