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1.
目的:探讨多药耐药基因(MDR1)多态性对乳腺癌紫杉联合蒽环类(TA)化疗疗效的预测价值.方法:利用PCR-RFLP技术对142例乳腺癌患者进行MDRl基因变异检测,观察其多态性分布;并对其中接受TA方案的具有完整疗效评价资料的63例新辅助化疗患者,开展MDR1 12外显子C1236T、21外显子G2677T/A和26外显子C3435T基因多态性与化疗疗效的相关分析.结果:C1236T、G2677T/A和C3435T在142例中国汉族乳腺癌女性人群中的变异频率分别为70.7%、55.0%和46.5%.其中,3435TT基因型在63例新辅助化疗患者中表现出与TA疗效的关联,其有效率(23.1%)显著低于携带C等位基因的患者(73.5%;X2=9.125,P=0.003).3个位点多态之间存在连锁不均衡性,携带3435C-2677G单体型的患者,化疗有效率(72.1%)高于其他单体型携带者(40.0%;X2=5.962,P=0.015),携带3435T-2677T或3435T-1236T单体型者,化疗有效率(54.3%或54.9%)低于对应的其他单体型携带者(82.4%和91.7%;X2=4.128和X2=4.118,P均为0.042);携带有3435T-2677T-1236T单体型者,化疗有效率(54.3%)低于其他单体型携带者(82.4%;X2=4.128,P=0.042).结论:MDR1 C3435T基因型及其与G2677T/A和(或)C1236T的单体型检测对于乳腺癌TA联合化疗疗效的预测具有重要参考价值.  相似文献   

2.
MDR1基因单核苷酸多态性与肝细胞肝癌预后的关系   总被引:1,自引:1,他引:0  
[目的]探讨多药耐药基因1(multidrug resistance gene 1,MDR1)C1236T及C3435T单核苷酸多态性(SNP)与肝细胞肝癌(HCC)预后间关系。[方法]以36例HCC根治术患者为对象,同时建立50例对照组,PCR-SSCP法检测其静脉血标本C1236T及C3435T SNP,比较分析C1236T及C3435T SNP与HCC预后的关系。[结果]HCC组与对照组的基因分布无统计学差异(P〉0.05)。C3435T基因型CC、CT、TT型中位无瘤生存时间依次为164.5d、340.0d和369.5d,C1236T基因型CC、CT、TT型中位无瘤生存时间依次为201.0d、415.0d、260.0d,MDR1基因多态性与HCC复发相关。[结论]C3435T SNP可作为肝癌根治术的预后因素之一。  相似文献   

3.
目的:探讨MDR1基因多态性与乳腺癌患者化疗疗效以及血液毒副反应的关系。方法:筛选70例新辅助化疗的女性患者,利用PCR-RFLP技术检测其外周血MDR1C3435T基因型,分析不同基因型患者化疗后的疗效及血液毒副反应。结果:70例新辅助化疗患者当中,3435TT基因型化疗有效率仅为23.1%,与3435CC和3435CT基因型相比差异有统计学意义(χ2=6.122,P=0.047,95%CI:0.043~0.051);血液毒性方面,3435CC型患者中性粒细胞Ⅲ~Ⅳ度减少的发生率为6.7%,较CT型(37.5%)和TT型(53.8%)发生率低(χ2=7.512,P=0.023,95%CI:0.016~0.021)。结论:携带MDR1 3435C等位基因的患者其化疗疗效可能较好;携带3435T等位基因的患者其中性粒细胞减少的风险可能较高。  相似文献   

4.
目的:探讨ApoA1-75G/A和+83C/T基因多态性与乳腺癌易感性之间的相关性。方法:研究对象为乳腺癌组217例,对照组221例。PCR-RFLP法检测ApoA1-75G/A和+83C/T基因多态性,采用SPSS13.0统计软件进行数据分析。结果:两组研究对象均存在ApoA1-75G/A和+83C/T基因多态性。ApoA1-75G/A多态性与乳腺癌发病,尤其是绝经前乳腺癌患者发病明显相关(OR=1.270,P=0.020;OR=1.445,P=0.003),与乳腺癌临床特征(肿瘤大小、淋巴结转移、病理分级以及雌孕激素受体状态)无明显相关。+83C/T多态性与乳腺癌发病明显相关(OR=1.517,P=0.005),与乳腺癌临床特征(月经状态、肿瘤大小、淋巴结转移、病理分级以及雌孕激素受体状态)无明显相关性。结论:ApoA1-75G/A和+83C/T基因多态性增加了乳腺癌发病的危险性,可能为乳腺癌发病的危险因素。  相似文献   

5.
目的:探讨人肺癌组织MDR1 C3435T和G2677T/A位点基因多态性与P-gp表达之间是否存在相关性.方法:免疫组化方法分析31例肺癌组织中P-gp的表达量,RFLP-PCR鉴定31例肺癌组织MDR1 C3435T和G2677T/A位点基因型.χ2检验分析基因型与P-gp表达量之间的关系.结果: 两位点基因型分布频率符合Hardy-weinberg平衡.免疫组化结果显示,P-gp表达量有较大差别.经χ2检验,C3435T位点基因型与P-gp表达有关,野生型与突变型和杂合型相比,差异有统计学意义,χ2=7.142,P=0.025.表达量趋势为C/C相似文献   

6.
目的:探讨MDR1基因多态性与其在乳腺癌患者癌组织中表达水平的关系。方法:筛选93例乳腺癌组织及26例配对癌旁组织,利用PCR-RFLP技术检测MDR1 exon12(1236)、exon21(2677)、exon26(3435)3个位点的多态性,以RT-qPCR技术对MDR1 mRNA进行相对定量,分析不同基因型患者间MDR1基因的表达水平。结果:93例乳腺癌组织中均有不同程度MDR1基因的表达;C1236T、G2677T/A和C3435T各基因型与MDR1表达水平之间均未显示统计学差异(F=0.047,P=0.954;F=0.364,P=0.833和F=0.173,P=0.841);但其中2 6例癌组织MDR1 mRNA表达水平,明显高于其对应的癌旁组织(3.83±5.27 vs 1.81±4.42;t=2.522,P=0.018)。结论:癌组织可能易发生多药耐药,MDR1表达差异的遗传学基础还有待进一步研究。  相似文献   

7.
目的:研究ABCB1 C3435T、G2677AT基因形态与癌痛患者疼痛感知的关系。方法:临床纳入2016年9月至2018年9月期间我院收治的185例恶性肿瘤患者组织病理学标本,将其中有癌痛的患者116例作为癌痛组,无癌痛的患者69例作为无痛组。应用三维聚丙烯酰胺凝胶DNA芯片技术检验患者ABCB1 C3435T、G2677AT基因分型情况,并分析ABCB1 C3435T、G2677AT基因形态与癌症患者癌痛的关系。结果:两组患者C3435T基因野生型、杂合子及突变型分布频率对比差异无统计学意义(P>0.05)。两组患者G2677AT基因野生型、杂合子及突变型分布频率对比差异无统计学意义(P>0.05)。疼痛程度不同的患者C3435T和G2677AT基因型分布频率无差异(P>0.05)。癌痛组患者C3435T与G2677AT不同基因型间组内对比NRS评分差异无统计学意义(P>0.05);C3435T与G2677AT相同基因型对比NRS评分差异无统计学意义(P>0.05)。结论:ABCB1 C3435T与G2677AT基因形态与癌痛患者疼痛感知并无直接关联,尚需进一步进行深入研究。  相似文献   

8.
目的:探讨多药耐药基因MDR1基因多态性在儿童急性淋巴细胞白血病(ALL)中的发生情况,及其与患儿长期生存的相关性。方法采用多重单碱基延伸单核苷酸多态性基因分型技术检测176例ALL患儿MDR1 C3435T、C1236T、G2677T/A位点的基因型分布特点,分析其与患儿长期(5年)生存的相关性。结果MDR1 C3435T中C/C、C/T、T/T基因型分别有67、94、15例;MDR1 C1236T中C/C、C/T、T/T基因型分别有23、82、71例;G2677T/A中G/T、T/T、T/A、G/G、G/A、A/A基因型分别有66、17、28、37、24、4例。本组176例患儿总体生存率为77.3%(136/176)。MDR1 C3435T中C/C、C/T、T/T基因型患儿的5年无事件生存(EFS)率分别为79.57%、83.33%、33.33%,其中携带T/T基因型患儿的5年EFS率低于携带C/C和C/T基因型的患儿(χ2=15.301,P=0.002)。 MDR1 C1236T中C/C、C/T、T/T基因型患儿的5年EFS分别为52.00%、81.71%、71.93%,其中携带C/C基因型患儿的5年EFS率低于携带C/T和T/T基因型的患儿(χ2=17.800,P=0.001)。结论 MDR1基因多态性与儿童ALL的EFS相关,携带MDR1 C3435T中T/T、MDR1 C1236T中C/C基因型的患儿长期生存率较低。  相似文献   

9.
目的 探讨醌氧化还原酶1 (quinone oxido-reductase 1,NQO1)基因C609T多态性和环境因素与乳腺癌遗传易感性的关系.方法 采用以医院为基础的病例对照研究收集桂林医学院附属医院2012-10-15-2014-02-15共248例女性乳腺癌患者和该院2013-03-01-2013-12-30共284名女性健康体检者的人口学和环境暴露资料等,并采用TaqManMGB荧光定量聚合酶链反应技术和多因素非条件Logistic回归模型分析NQO1基因C609T在两组中分布频率的差异,以及与环境因素的交互作用.结果 病例组NQO1基因位点CC、CT和TT各基因型频率分别为27.42%、49.60%和22.98%,对照组中基因型频率分别为34.51%、50.35%和15.14%,差异有统计学意义,x2 =6.48,P=0.039.多因素Logistic回归分析表明,与CC基因型相比,CT或TT基因型的个体罹患乳腺癌的风险OR值分别为1.33和2.92.病例组等位基因T频率(47.78%)较对照组(40.32%)增高(x2=6.00,P=0.014),携带T等位基因者患乳腺癌的危险性是C等位基因携带者的1.36倍.交互作用分析表明,NQO1基因C609T多态性与经常熬夜、被动吸烟、精神创伤、睡觉佩戴胸罩、性格和体育锻炼等之间均存在交互作用(P<0.05),其OR值分别为2.45、3.96、2.40、1.98、0.33和0.52.结论 NQO1基因C609T多态性可能为乳腺癌发病的遗传易感因素,且与环境因素具有协同致癌作用.  相似文献   

10.
李建国  焦玮  王宇  柳晓义 《肿瘤》2011,31(3):261-263
目的:探讨肿瘤抑制基因Ras相关区域家族1A基因(Ras association domain family 1A gene, RASSF1A)第3外显子G435T多态性与乳腺癌发病的相关性。方法:采用聚合酶链反应-单链构象多态性分析(PCR-single strand conformation polymorphism analysis, PCR-SSCP)法检测212例乳腺癌患者、218例乳腺良性病变患者,及220例健康对照人群RASSF1A 基因 G435T的多态性,并分析RASSF1A基因多态性与乳腺癌易感性的相关性。结果:RASSF1A基因 G435T位点的TG+TT基因型及T等位基因的频率乳腺癌组明显高于乳腺良性病变组和健康对照人群组2个对照组。而乳腺良性病变组与健康对照人群组之间,则差异无统计学意义;结论:RASSF1A基因第3外显子G435T位点G/T多态性可能为乳腺癌发病的易感基因位点,T等位基因可能乳腺癌发病的易感基因位点。  相似文献   

11.
BACKGROUND: The MDR1 gene encodes P-glycoprotein (PGP), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. Polymorphisms in the MDR1 gene may have an impact on the expression and function of PGP, thereby influencing the response to chemotherapy. METHODS: We investigated the potential association of MDR1 polymorphisms (2677G>T at exon 21 and 3435C>T at exon 26) and their haplotypes with chemotherapy response in 54 small cell lung cancer (SCLC) patients who received a combination chemotherapy of etoposide-cisplatin. RESULTS: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotype (P = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Consistent with the results of genotyping analyses, patients harboring the 2677G-3435C haplotype had a statistically significant better response to chemotherapy compared with those with the other haplotypes combined (P = 0.015). CONCLUSIONS: Our findings suggest that the MDR1 2677G>T and 3435C>T polymorphisms can be used for predicting treatment response to etoposide-cisplatin chemotherapy in SCLC patients.  相似文献   

12.
Background: P-glycoprotein (P-gp), a membrane transporter encoded by the multidrug resistance-1 (MDR1) gene,influences pharmacokinetics and metabolism of anticancer drugs and contributes to multidrug resistance phenotypein acute lymphoblastic leukemia (ALL). Genetic variation ofMDR1 in ALL patients is increasingly recognized asa factor influencing response to treatment. Aim: To investigate the possible role of MDR-1 gene polymorphisms(C3435T, C1236T and C4125A) as risk factors for the development and clinical outcome of ALL in Egyptian children.Materials and Methods: Genotyping of MDR-1 C3435T, C1236T and C4125A single nucleotide polymorphisms(SNPs) was accomplished using a polymerase chain reaction–restriction fragment length polymorphism (RFLP-PCR)assay with 120 childhood ALL patients and 100 healthy controls. Results: Homozygous T with the C3435T SNP showeda protective effect as compared to homozygous C (OR=0.748) while heterozygous CT correlated with a poor outcome(high risk, drug unresponsiveness, relapse and high percentage of death). Additionally, the T allele of the C1236T SNPshowed a significant relation with ALL risk (OR=1.6). However, there were no significant differences in the genotypeand allele frequencies of MDR-1 SNPs between patients and controls. Only one genotype (CC) and one allele ofMDR-1 (C4125A) were seen. Neither CA/AA genotypes nor A alleles were present in ALL patients and normal controls.TC was the predominant haplotype in both groups, while CT proved to be minor. The cumulative incidence of relapsewas higher with the CC genotype of C1236T as compared with TT. Conclusion: From our preliminary data, the CTgenotype of C3435T is associated with a poor ALL outcome while the CC genotype of C1236T is related with anincreased incidence of relapse. Although our results provide assistance for oncologist choice of individual therapeuticstrategy taking the patient genetic repertoire into consideration, further investigations with larger sample size shouldbe conducted to validate our results.  相似文献   

13.
The human multidrug resistance gene (MDR1, ABCB1) codes for P-glycoprotein (P-gp) that affects the pharmacokinetics of many drugs. MDR1 single nucleotide polymorphisms (SNPs) are associated with drug clearance. Imatinib is a substrate of P-gp-mediated efflux. We investigated the MDR1 T1236C, G 2677T/A, and C3435T polymorphism in 52 patients with chronic myeloid leukemia treated with imatinib. The distribution of MDR1 1236, 2677, or 3435 genotypes was significantly different between the resistance patients and sensitivity patients. The resistance incidence correlated with the number of T alleles at locus 1236 and 3435. Resistance was higher for patients homozygous for the 1236T allele when compared to patients with CT/CC genotype groups (75% vs. 31.3%, P = 0.004). For the G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with genotype AG/AT/AA, when compared to other genotype groups (TT/GT/GG, P = 0.02). Patients with 3435 TT/CT genotypes showed a higher resistance when compared with patients with CC genotype (59.4% vs. 25%, P = 0.023). In conclusion, determination of 1236T, C3435T, and G2677T MDR1 polymorphisms might be useful in response prediction to therapy with imatinib in patients with CML.  相似文献   

14.
Hur EH  Lee JH  Lee MJ  Choi SJ  Lee JH  Kang MJ  Seol M  Jang YE  Lee HJ  Kang IS  Shim SK  Ryu SG  Kang YA  Lee YS  Park CJ  Chi HS  Lee KH 《Leukemia research》2008,32(10):1601-1604
We investigated the association between the MDR1 C3435T polymorphism and P-glycoprotein function of leukemic blasts as well as clinical outcomes in 200 patients with AML, excluding the M3 subtype. The CC, CT and TT genotype frequencies of the C3435T polymorphism among patients were 71, 93 and 36, respectively. The C3435T polymorphism genotypes did not have influence on the P-glycoprotein function of leukemic blasts. Complete remission rates and overall, relapse-free and event-free survival rates were not significantly different among the C3435T polymorphism genotypes. In conclusion, the MDR1 C3435T polymorphism does not appear to have significant clinical implications in AML.  相似文献   

15.
Han JY  Lim HS  Yoo YK  Shin ES  Park YH  Lee SY  Lee JE  Lee DH  Kim HT  Lee JS 《Cancer》2007,110(1):138-147
BACKGROUND: The authors investigated whether ABCB1, ABCC2, and ABCG2 genetic polymorphisms affect pharmacokinetics (PK) of irinotecan and treatment outcome of patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Blood samples from 107 NSCLC patients treated with irinotecan and cisplatin chemotherapy were used for genotyping ABCB1 (1236C > T, 2677G > T/A, 3435C > T), ABCC2 (-24C > T, 1249G > A, 3972C > T), and ABCG2 (34G > A, 421C > A) polymorphisms. Genotypes were correlated with irinotecan-PK, toxicity, tumor response, and survival. RESULTS: Among 8 polymorphisms, 3435TT and 2677TT were associated with AUC(SN-38G) and CL(SN-38G). When haplotypes are assigned, 2677TT/3435TT carriers showed significantly lower AUC(SN-38G) (P = .006), whereas 2677GG/3435CC carriers showed significantly higher AUC(SN-38) (P = .039). These findings suggest that 2677TT and 3435TT variants are associated with higher efflux activity. In toxicity, the 2677G/T or A was associated with grade 4 neutropenia. The 2677GG carriers showed significantly lower absolute neutrophil count during the 1(st) cycle (P = .012) as well as entire course of chemotherapy (P = .042). The 3435TT was associated with higher frequency of grade 3 diarrhea (P = .047). In tumor response, ABCC2 -24TT and 3972TT genotypes were associated with higher response rates (P = .031 and .046, respectively) and longer progression-free survival (P = .035 and .038, respectively), which was sustained in haplotype analysis. CONCLUSIONS: Specific polymorphisms of ABCB1 and ABCC2 can influence disposition and tumor response to irinotecan by regulating transporter activity. These findings may help to individualize irinotecan-based chemotherapy in patients with advanced NSCLC.  相似文献   

16.
Expression of the adenosine triphosphate‐binding cassette B1 (ABCB1) transporter and P‐glycoprotein are associated with resistance to anticancer drugs. The purpose of this study was to investigate the role of single nucleotide polymorphism in the ABCB1 and CYP3A genes in breast cancer patients who were treated with neoadjuvant chemotherapy. Stage II/III breast cancer patients were treated with three cycles of neoadjuvant, after which the patients received curative surgery and adjuvant chemotherapy. The polymorphisms of ABCB1 and CYP3A were genotyped. The correlation of polymorphism of ABCB1, CYP3A, and clinical outcomes was analyzed. Among the 216 patients, ABCB1 3435TT genotype had a longer overall survival (OS). than CC/CT. Multivariate analyses demonstrated that good PS, invasive ductal carcinoma, non‐triple negative phenotype and initial operable stage were significantly associated with a lower death risk. ABCB1 3435TT genotype had a higher AUC than CC/CT for docetaxel. These higher AUCs in the C3435TT was associated with increased toxicities of neutropenia and diarrhea. This study showed that the genetic polymorphism of ABCB1 C3435T might be associated with a longer OS. Our results also suggest that the prediction of docetaxel toxicity might be possible for C3435T polymorphism. This study results provides valuable information on individualized therapy according to genotypes.  相似文献   

17.
Multidrug resistance protein 1 (MDR1, Pgp, ABCB1) is a membrane efflux transporter protein encoded by the MDR1 gene. The overexpression of this gene has been linked with the resistance to a variety of cancer chemotherapeutic agents in cancer patients. It also has an important role in tissue and cell defense against xenobiotics and toxic-compounds insult. A gene polymorphism in exon 26 of MDR1 (C3435T) has been reported to be associated with a decreased expression of MDR1 in TT genotype carriers compared with those of the CC genotype. In the present study, the MDR1 C3435T polymorphism of an ethnic Iranian population with acute lymphoblastic leukemia (ALL) was studied, and the incidence of the genotypes was compared among patients in different age groups: ≥ 20 years of age (A) and 1-19 years of age (B). The percent distribution of genotypes were found to be TT (A: 21.4; B: 26.0), TC (A: 57.1; B: 60.0), and CC (A: 21.4; B: 14.0). The B group ALL patients (1-19 years) were further divided into 2 groups of 1-9 (Y) and 9-19 (Z) years of age, and their MDR1 C3435T genotypes were analyzed. The distribution of the genotypes were found to be as follows: TT (Y: 27.9; Z: 23.1), TC (Y: 60.7.1; Z: 59.0), and CC (Y: 11.5; Z: 17.9). No significant differences were found among different genotypes in the studied age groups. It was concluded that in the studied population no specific genotype (either TT, TC, or CC) in MDR1 C3435T gene polymorphism was associated with the incidence of ALL. Further studies will shed light on the possible importance of these findings.  相似文献   

18.
PURPOSE: Polymorphisms that are associated with ABCB1 expression and function may be linked to treatment efficacy and the development of neutropenia and neurotoxicity in patients with androgen-independent prostate cancer receiving docetaxel. EXPERIMENTAL DESIGN: Patients with androgen-independent prostate cancer treated with docetaxel alone (n = 23) or docetaxel and thalidomide (n = 50) were genotyped for the ABCB1 1236C>T, 2677 G>T/A, and 3435 C>T alleles by direct sequencing, and diplotypes were constructed using an EM algorithm. The data were then compared with duration to onset of peripheral neuropathy, neutropenia grade, and survival after docetaxel. RESULTS: For patients receiving docetaxel alone, individuals carrying a diplotype consisting of the 1236C-2677G-3435C linked alleles had improved overall survival after treatment (P = 0.0017). Additionally, patients treated with docetaxel and thalidomide carrying a diplotype consisting of the 2677T-3435T haplotype had a shorter median survival (P = 0.045). After adjusting for a particular set of polymorphisms and diplotype groupings, a hazard ratio of 10.87 was found for patients carrying the 2677GG genotype versus patients carrying other genotypes (P = 0.0048) in the docetaxel and thalidomide cohort. Among both treatment arms together, individuals carrying the 2677GG genotype also had a significantly longer time to neuropathy (P = 0.035). Finally, there was a strong trend toward patients carrying the 2677TT-3435TT diplotype having higher grades of neutropenia (P = 0.053). CONCLUSION: The data suggest that docetaxel-induced neuropathy, neutropenia grade, and overall survival could be linked to ABCB1 allelic variants with ensuing negative implications for docetaxel treatment in patients carrying ABCB1 variant genotypes.  相似文献   

19.
The multidrug resistance (MDR1) gene product P-glycoprotein is a membrane bound protein that functions as an ATP-dependent efflux pump, transporting exogenous and endogenous substrates from the cells. Since it plays an important role in chemotherapy, there is an increasing interest in the possible significance of genetic variation in MDR1. Our main objective was to study the MDR1gene polymorphism at C3435T with reference to development and progression of acute leukemia. The present study included 290 acute leukemia cases, comprising of 147 acute lymphocytic leukemia (ALL), 143 acute myeloid leukemia and 249 age-sex matched control samples for the analysis of MDR1 C3435T polymorphism, by the PCR-RFLP method. The MDR1 genotype distribution revealed an elevated frequency of the TT genotype in ALL cases (51.7%) as compared to controls (28.9%), whereas AML group did not show any association. The mean white blood cell count, blast% and LDH levels were increased in ALL patients with the CC genotype. No deviation was observed with respect to haemoglobin, platelet count and disease free survival in ALL patients. The association of CC genotype with clinical variables in ALL indicated that the CC genotype with high expression might be eliminating antileukemic drugs (anthracyclines, Daunorubicin, Vincristeine, Mitoxanthrone) which are P-gp substrates, leading to lower intra cellular drug concentrations and a poor prognosis. Such an association with the CC genotype was not observed in AML. In conclusion, these results suggested that the MDR1 TT genotype might influence risk of development of acute lympoblastic leukemia and the CC genotype might be linked to a poor prognosis of ALL.  相似文献   

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