BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries....BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.展开更多
Hypermethylation in the promoter region of tumor suppressor genes is a common mechanism of gene silencing, which tends to occur in cancer. The effects of 5-Aza-2＇-deoxycytidine （5-Aza-CdR）, a specific DNA methyltra...Hypermethylation in the promoter region of tumor suppressor genes is a common mechanism of gene silencing, which tends to occur in cancer. The effects of 5-Aza-2＇-deoxycytidine （5-Aza-CdR）, a specific DNA methyltransferase inhibitor, on the cell proliferation of human breast cancer cell line MCF-7 and on the expression of Apaf-1 gene were investigated. Human MCF-7 cells were incubated with increasing concentrations of 5-Aza-CdR for 12 to 120 h. The growth inhibition rates of MCF-7 cells were detected by MTT assay. Changes of cell cycle distribution and apoptotic rates of MCF-7 cells were determined by flow cytometry. The expressions of DNA methyltransferase 3b mRNA and Apaf-1 mRNA were measured by reverse transcription polymerase chain reaction （RT-PCR）. Meanwhile, the expression of Apaf-1 protein was detected by Western blotting. The results showed that 5-Aza-CdR significantly inhibited the growth of MCF-7 cells and the growth inhibition rate of MCF-7 cells was significantly enhanced with the concentration of 5-Aza-CdR and the action time. Flow cytometry indicated that 5-Aza-CdR could significantly induce G1/S cell cycle arrest and increase the apoptosis rate of MCF-7 cells. The mRNA and protein expressions of Apaf-1 were up-regulated in MCF-7 cells treated with 5-Aza-CdR, which was accompanied by down-regulation of DNA methyltransferase 3b mRNA. It is concluded that 5-Aza-CdR might retard the growth of tumor ceils and promote the apoptosis of MCF-7 breast cancer cells by inhibiting the expression of DNA methyltransferase 3b and re-activating the Apaf-1 gene expression.展开更多
BACKGROUND The clinical significance of breast cancer susceptibility gene 1(BRCA1)in nonsmall cell lung cancer(NSCLC)patients undergoing surgery remains unclear up to now.AIM To explore the relation of BRCA1 expressio...BACKGROUND The clinical significance of breast cancer susceptibility gene 1(BRCA1)in nonsmall cell lung cancer(NSCLC)patients undergoing surgery remains unclear up to now.AIM To explore the relation of BRCA1 expression with clinicopathological characteristics and survival in patients with resected NSCLC.METHODS EMBASE,PubMed,Web of Science,and The Cochrane Library databases were searched to identify the relevant articles.To assess the correlation between the expression of BRCA1 and clinicopathological characteristics and prognosis of patients with resected NSCLC patients,the combined relative risks or hazard ratios(HRs)with their corresponding 95%confidence intervals[CIs]were estimated.RESULTS Totally,11 articles involving 1041 patients were included in the meta-analysis.The results indicated that the expression of BRCA1 was significantly correlated with prognosis of resected NSCLC.Positive BRCA1 expression signified a shorter overall survival(HR=1.60,95%CI:1.25-2.05;P<0.001)and disease-free survival(HR=1.78,95%CI:1.42-2.23;P<0.001).However,no significant association of BRCA1 expression with any clinicopathological parameters was observed.CONCLUSION BRCA1 expression indicates a poor prognosis in resected NSCLC patients.BRCA1 might serve as an independent biomarker to predict clinical outcomes and help to customize optimal adjuvant chemotherapy for NSCLC patients who had received surgical therapy.展开更多
Associations of null polymorphism (copy number variation) of detoxification genes GSTM1, GSTT1 and GSTP1 (at rs2495636, 105 Ile/Val) with the breast cancer (BC) were assessed in two main ethnic groups of the Republic ...Associations of null polymorphism (copy number variation) of detoxification genes GSTM1, GSTT1 and GSTP1 (at rs2495636, 105 Ile/Val) with the breast cancer (BC) were assessed in two main ethnic groups of the Republic of Kazakhstan (Kazakhs and Russians). Total number of patients was 181, and of controls 397. Statistically significant difference was observed between BC patients and healthy individuals in alleles frequency (χ2 = 4.89, р = 0.007) of GSTP1 gene at rs2495636 (105 Ile/Val) among the Kazakhs ethnic group. Difference in genotypes distribution (χ2 =5.26, р = 0.076) at this site is approximating to be statistically significant. In the Russian group, no differences were found in genotypes and alleles atrs 2495636 of GSTP1 gene between cases and controls. There was no significant difference between null polymorphism (copy number variation) of GSTM1 and GSTT1 genes among cases and controls in both ethnic groups.展开更多
Breast cancer gene 1(BRCA1) gene was the first breast cancel susceptibility gene discovered in familial breast cancer.It has been revealed that BRCA1 can be combined with an array of important protein involved in cell...Breast cancer gene 1(BRCA1) gene was the first breast cancel susceptibility gene discovered in familial breast cancer.It has been revealed that BRCA1 can be combined with an array of important protein involved in cell cycle regulation,DNA repair,gene transcription control and apoptosis regulation.It plays a down-regulation effect on tumor growth and an important role in maintaining genomic stability.New research suggests that it also associate with the breast cancer stem cells and microRNA.Its mutations,promoter methylation and ectopic expression may one of the main reasons for the generation and development of hereditary breast cancer.展开更多
目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene...目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene expression omnibus,GEO)的子数据集GSE4290,GSE90598,分析BAP1在正常组织及胶质瘤组织中的差异性表达情况;受试者工作特征(receiver operating characteristic,ROC)曲线分析BAP1对恶性胶质瘤的早期诊断价值;选取自主收集的非配对28例恶性胶质瘤患者的原发灶组织、5例颅脑外伤患者内减压术切除的非瘤脑组织,采用实时荧光定量PCR(quantitative real-time polymerase chain reaction,qRT-PCR)检测BAP1的表达水平;利用靶向BAP1的特异性小干扰RNAs(small interfering RNAs,siRNAs)瞬时转染U251细胞系,进一步检测其干涉效率;基于流式细胞仪分析BAP1下调的U251细胞系,其细胞周期、凋亡的变化情况。结果生物信息学结果显示,BAP1在恶性胶质瘤组织中的表达水平均低于正常脑组织(GSE4290:1209±18.49 vs 1476±53.90;GSE90598:5.19±0.10 vs 5.65±0.21),差异具有统计学意义(t=5.115,2.267,均P<0.05)。ROC曲线显示,BAP1可高效区分恶性胶质瘤组织与正常脑组织(GSE4290:AUC=0.78;GSE90598:AUC=0.75,均P<0.05)。临床标本结果显示,BAP1在恶性胶质瘤原发灶组织中的表达水平显著低于非瘤脑组织(0.27±0.04 vs 1.06±0.07),差异具有统计学意义(t=10.22,P<0.001)。在U251细胞系中下调BAP1的表达,其细胞周期中S期细胞比例明显增多,由17.59%分别增至27.21%(siBAP1-1)和25.79%(siBAP1-2),差异具有统计学意义(t=6.576,6.642,均P<0.01),而细胞凋亡水平则有所下降,由10.17%分别降至2.70%(siBAP-1)和3.00%(siBAP-2),差异具有统计学意义(t=10.31,9.428,均P<0.01)。结论组蛋白H2A去泛素化酶BAP1能够通过抑制恶性胶质瘤细胞周期快速进展并促进其凋亡,进而发挥肿瘤抑癌基因的功能,可作为潜在的恶性胶质瘤临床诊断标志物。展开更多
乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)是著名的肿瘤易感基因,它编码的蛋白质在正确修复受损DNA中起至关重要的作用。目前国内外关于BRCA1的报道多集中在乳腺癌和卵巢癌的遗传易感性方面,关于BRCA1在结直肠癌(col...乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)是著名的肿瘤易感基因,它编码的蛋白质在正确修复受损DNA中起至关重要的作用。目前国内外关于BRCA1的报道多集中在乳腺癌和卵巢癌的遗传易感性方面,关于BRCA1在结直肠癌(colorectal cancer,CRC)中的效用知之甚少,本文将综述BRCA1基因突变、mRNA及蛋白表达与CRC关系的研究进展及其潜在的治疗作用。展开更多
目的探讨自主运动训练在乳腺癌发生发展中的作用及其机制。方法将携带原发性人乳腺癌基因1(breast cancer gene 1,BRCA-1)突变基因的癌细胞在体外进行培养,用连续14 d自主跑轮运动鼠血清以及静坐鼠血清处理BRCA-1突变肿瘤细胞,并将上述...目的探讨自主运动训练在乳腺癌发生发展中的作用及其机制。方法将携带原发性人乳腺癌基因1(breast cancer gene 1,BRCA-1)突变基因的癌细胞在体外进行培养,用连续14 d自主跑轮运动鼠血清以及静坐鼠血清处理BRCA-1突变肿瘤细胞,并将上述条件血清培养的乳腺癌细胞注射到BALB/c裸鼠皮下,观察经过不同处理后体内外BRCA-1突变乳腺癌细胞及移植瘤的情况。结果在体外,与静坐鼠血清处理组相比,自主运动鼠血清处理后抑制了BRCA-1突变乳腺癌细胞的活力、生长,促进其凋亡,差异具有统计学意义(P<0.05);在体内,自主运动鼠血清培养的BRCA-1突变乳腺癌细胞移植瘤较静坐对照组体积减小、生长缓慢(P<0.05),体内外自主运动组均呈现出增强的Caspase-3活性(P<0.05)。结论自主跑轮运动可能通过增强Caspase3的活性、抑制了BRCA1突变乳腺癌细胞以及其在BALB/c裸鼠皮下异种移植瘤的增殖、促进肿瘤细胞凋亡,从而抑制其体内外的生长。展开更多
文摘BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.
文摘Hypermethylation in the promoter region of tumor suppressor genes is a common mechanism of gene silencing, which tends to occur in cancer. The effects of 5-Aza-2＇-deoxycytidine （5-Aza-CdR）, a specific DNA methyltransferase inhibitor, on the cell proliferation of human breast cancer cell line MCF-7 and on the expression of Apaf-1 gene were investigated. Human MCF-7 cells were incubated with increasing concentrations of 5-Aza-CdR for 12 to 120 h. The growth inhibition rates of MCF-7 cells were detected by MTT assay. Changes of cell cycle distribution and apoptotic rates of MCF-7 cells were determined by flow cytometry. The expressions of DNA methyltransferase 3b mRNA and Apaf-1 mRNA were measured by reverse transcription polymerase chain reaction （RT-PCR）. Meanwhile, the expression of Apaf-1 protein was detected by Western blotting. The results showed that 5-Aza-CdR significantly inhibited the growth of MCF-7 cells and the growth inhibition rate of MCF-7 cells was significantly enhanced with the concentration of 5-Aza-CdR and the action time. Flow cytometry indicated that 5-Aza-CdR could significantly induce G1/S cell cycle arrest and increase the apoptosis rate of MCF-7 cells. The mRNA and protein expressions of Apaf-1 were up-regulated in MCF-7 cells treated with 5-Aza-CdR, which was accompanied by down-regulation of DNA methyltransferase 3b mRNA. It is concluded that 5-Aza-CdR might retard the growth of tumor ceils and promote the apoptosis of MCF-7 breast cancer cells by inhibiting the expression of DNA methyltransferase 3b and re-activating the Apaf-1 gene expression.
文摘BACKGROUND The clinical significance of breast cancer susceptibility gene 1(BRCA1)in nonsmall cell lung cancer(NSCLC)patients undergoing surgery remains unclear up to now.AIM To explore the relation of BRCA1 expression with clinicopathological characteristics and survival in patients with resected NSCLC.METHODS EMBASE,PubMed,Web of Science,and The Cochrane Library databases were searched to identify the relevant articles.To assess the correlation between the expression of BRCA1 and clinicopathological characteristics and prognosis of patients with resected NSCLC patients,the combined relative risks or hazard ratios(HRs)with their corresponding 95%confidence intervals[CIs]were estimated.RESULTS Totally,11 articles involving 1041 patients were included in the meta-analysis.The results indicated that the expression of BRCA1 was significantly correlated with prognosis of resected NSCLC.Positive BRCA1 expression signified a shorter overall survival(HR=1.60,95%CI:1.25-2.05;P<0.001)and disease-free survival(HR=1.78,95%CI:1.42-2.23;P<0.001).However,no significant association of BRCA1 expression with any clinicopathological parameters was observed.CONCLUSION BRCA1 expression indicates a poor prognosis in resected NSCLC patients.BRCA1 might serve as an independent biomarker to predict clinical outcomes and help to customize optimal adjuvant chemotherapy for NSCLC patients who had received surgical therapy.
文摘Associations of null polymorphism (copy number variation) of detoxification genes GSTM1, GSTT1 and GSTP1 (at rs2495636, 105 Ile/Val) with the breast cancer (BC) were assessed in two main ethnic groups of the Republic of Kazakhstan (Kazakhs and Russians). Total number of patients was 181, and of controls 397. Statistically significant difference was observed between BC patients and healthy individuals in alleles frequency (χ2 = 4.89, р = 0.007) of GSTP1 gene at rs2495636 (105 Ile/Val) among the Kazakhs ethnic group. Difference in genotypes distribution (χ2 =5.26, р = 0.076) at this site is approximating to be statistically significant. In the Russian group, no differences were found in genotypes and alleles atrs 2495636 of GSTP1 gene between cases and controls. There was no significant difference between null polymorphism (copy number variation) of GSTM1 and GSTT1 genes among cases and controls in both ethnic groups.
文摘Breast cancer gene 1(BRCA1) gene was the first breast cancel susceptibility gene discovered in familial breast cancer.It has been revealed that BRCA1 can be combined with an array of important protein involved in cell cycle regulation,DNA repair,gene transcription control and apoptosis regulation.It plays a down-regulation effect on tumor growth and an important role in maintaining genomic stability.New research suggests that it also associate with the breast cancer stem cells and microRNA.Its mutations,promoter methylation and ectopic expression may one of the main reasons for the generation and development of hereditary breast cancer.
文摘目的探索乳腺癌/卵巢癌易感基因1相关蛋白1(breast/ovarian cancer susceptibility gene 1 associated protein 1,BAP1)对人源恶性胶质瘤发生、发展的作用与BAP1作为恶性胶质瘤临床诊断标志物的可行性。方法基于基因表达综合数据库(gene expression omnibus,GEO)的子数据集GSE4290,GSE90598,分析BAP1在正常组织及胶质瘤组织中的差异性表达情况;受试者工作特征(receiver operating characteristic,ROC)曲线分析BAP1对恶性胶质瘤的早期诊断价值;选取自主收集的非配对28例恶性胶质瘤患者的原发灶组织、5例颅脑外伤患者内减压术切除的非瘤脑组织,采用实时荧光定量PCR(quantitative real-time polymerase chain reaction,qRT-PCR)检测BAP1的表达水平;利用靶向BAP1的特异性小干扰RNAs(small interfering RNAs,siRNAs)瞬时转染U251细胞系,进一步检测其干涉效率;基于流式细胞仪分析BAP1下调的U251细胞系,其细胞周期、凋亡的变化情况。结果生物信息学结果显示,BAP1在恶性胶质瘤组织中的表达水平均低于正常脑组织(GSE4290:1209±18.49 vs 1476±53.90;GSE90598:5.19±0.10 vs 5.65±0.21),差异具有统计学意义(t=5.115,2.267,均P<0.05)。ROC曲线显示,BAP1可高效区分恶性胶质瘤组织与正常脑组织(GSE4290:AUC=0.78;GSE90598:AUC=0.75,均P<0.05)。临床标本结果显示,BAP1在恶性胶质瘤原发灶组织中的表达水平显著低于非瘤脑组织(0.27±0.04 vs 1.06±0.07),差异具有统计学意义(t=10.22,P<0.001)。在U251细胞系中下调BAP1的表达,其细胞周期中S期细胞比例明显增多,由17.59%分别增至27.21%(siBAP1-1)和25.79%(siBAP1-2),差异具有统计学意义(t=6.576,6.642,均P<0.01),而细胞凋亡水平则有所下降,由10.17%分别降至2.70%(siBAP-1)和3.00%(siBAP-2),差异具有统计学意义(t=10.31,9.428,均P<0.01)。结论组蛋白H2A去泛素化酶BAP1能够通过抑制恶性胶质瘤细胞周期快速进展并促进其凋亡,进而发挥肿瘤抑癌基因的功能,可作为潜在的恶性胶质瘤临床诊断标志物。
文摘目的探讨自主运动训练在乳腺癌发生发展中的作用及其机制。方法将携带原发性人乳腺癌基因1(breast cancer gene 1,BRCA-1)突变基因的癌细胞在体外进行培养,用连续14 d自主跑轮运动鼠血清以及静坐鼠血清处理BRCA-1突变肿瘤细胞,并将上述条件血清培养的乳腺癌细胞注射到BALB/c裸鼠皮下,观察经过不同处理后体内外BRCA-1突变乳腺癌细胞及移植瘤的情况。结果在体外,与静坐鼠血清处理组相比,自主运动鼠血清处理后抑制了BRCA-1突变乳腺癌细胞的活力、生长,促进其凋亡,差异具有统计学意义(P<0.05);在体内,自主运动鼠血清培养的BRCA-1突变乳腺癌细胞移植瘤较静坐对照组体积减小、生长缓慢(P<0.05),体内外自主运动组均呈现出增强的Caspase-3活性(P<0.05)。结论自主跑轮运动可能通过增强Caspase3的活性、抑制了BRCA1突变乳腺癌细胞以及其在BALB/c裸鼠皮下异种移植瘤的增殖、促进肿瘤细胞凋亡,从而抑制其体内外的生长。
