本文選題：COMT + 多態(tài)性�。� 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:不同分子分型的乳腺癌具有不同的治療及預(yù)后,化療是乳腺癌治療的重要手段之一,現(xiàn)有的研究證據(jù)表明乳腺癌化療后存在不同程度的認(rèn)知功能障礙,而COMT、APOE和BDNF基因的不同表達(dá)與認(rèn)知功能密切相關(guān)。乳腺癌化療后認(rèn)知功能障礙的發(fā)生是否與其COMT、APOE和BDNF基因多態(tài)性有關(guān),目前尚不清楚。目的:探討三陰性乳腺癌COMT、APOE和BDNF基因多態(tài)性與其化療后認(rèn)知功能障礙發(fā)生的相關(guān)性。方法:分別對(duì)80例三陰性和165例年齡、教育程度相匹配的非三陰性乳腺癌患者化療前后進(jìn)行認(rèn)知神經(jīng)性心理學(xué)量表測(cè)查,包括前瞻性記憶(Prospective memory,PM)和回顧性記憶(Retrospective memory,RM)問卷調(diào)查。對(duì)入組對(duì)象進(jìn)行COMT(rs165599,rs4680,rs737865),APOE(rs429358,rs7412)和BDNF(rs6265)6個(gè)單核苷多態(tài)性(SNP)位點(diǎn)的基因檢測(cè),同時(shí)分析各個(gè)基因位點(diǎn)和化療后認(rèn)知功能障礙的相關(guān)性。結(jié)果:1)乳腺癌患者化療前后總體認(rèn)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),差異具有的統(tǒng)計(jì)學(xué)意義(z=-2.942,z=-4.62,z=-7.87;p0.01);乳腺癌患者化療前后RM問卷調(diào)查(16.23±4.03 vs.17.21±4.59)和PM問卷調(diào)查(16.01±4.64 vs.18.20±4.51),差異具有統(tǒng)計(jì)學(xué)意義(z=-3.37,t=-5.32;p0.01);2)與非三陰性乳腺癌患者相比,三陰性乳腺癌患者化療后在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)得分上均明顯低于非三陰性乳腺癌,差異具有的統(tǒng)計(jì)學(xué)意義(z=-3.74,t=-5.88,t=-9.64;p0.01)。三陰性乳腺癌患者化療后RM問卷調(diào)查(19.10±2.36),明顯高于非三陰組(16.29±5.10),差異具有統(tǒng)計(jì)學(xué)意義(z=-5.33;p0.01);三陰性乳腺癌患者PM問卷調(diào)查(20.44±3.41),明顯高于非三陰組(17.12±4.58),差異具有統(tǒng)計(jì)學(xué)意義(z=-5.99;p0.01)。3)所檢測(cè)的6個(gè)SNP位點(diǎn)中,乳腺癌患者COMT(rs165599)位點(diǎn)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)較G/G基因型顯著降低認(rèn)知功能損害發(fā)生的幾率。而兩組乳腺癌患者上的APOE(rs429358,rs7412)及BDNF(rs6265)均未發(fā)現(xiàn)統(tǒng)計(jì)學(xué)差異。4)進(jìn)一步分析COMT(rs165599)位點(diǎn)和化療后認(rèn)知功能障礙的相關(guān)性,發(fā)現(xiàn)顯性模型(dominant model,β=-1.441,95%CI=-2.781~-0.101)與回顧性記憶成績(jī)顯著相關(guān)。結(jié)論:三陰性乳腺癌化療后認(rèn)知功能障礙較非三陰乳腺癌患者重,并且COMT(rs165599)位點(diǎn)與RM成績(jī)呈線性相關(guān),提示三陰性乳腺癌患者COMT基因多態(tài)性可能是化療后認(rèn)知功能障礙的遺傳學(xué)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. 緇撴灉:1)涔寵吅鐧屾?zhèn)ｈ�呭寲鐤楀墠鍚庢，

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