目的评价不同人群UGT1A1基因GLY71ARG多态性、TATA重复多态性与新生儿黄疸的遗传关联性。方法 制定原始文献的纳入标准、排除标准及检索策略,检索PubMed、EMBASE、Web of sciences、Cochrance图书馆、中国期刊全文数据库、万方数据库...目的评价不同人群UGT1A1基因GLY71ARG多态性、TATA重复多态性与新生儿黄疸的遗传关联性。方法 制定原始文献的纳入标准、排除标准及检索策略,检索PubMed、EMBASE、Web of sciences、Cochrance图书馆、中国期刊全文数据库、万方数据库、维普中文科技期刊数据库及中国生物医学文献数据库,检索时间均为建库至2010年2月。获得UGT1A1基因GLY71ARG多态性、TATA重复多态性与新生儿黄疸遗传关联性的相关文献。以新生儿黄疸为病例组。依据NHI-NHGRI研究工作组2007年制定的遗传关联性研究报告规范为基础,并依据相关文献选取其中的14条标准用于文献质量评价。以基因型和等位基因频率为指标,采用RevMan 5.0软件进行Meta分析,计算合并的OR值及其95%CI。结果共检索到相关文献284篇,22篇文献进入Meta分析(英文文献18篇,中文文献4篇);病例组1444例,对照组1 835例。按人群构成分为4个亚组:中国,日本,马来西亚和泰国及高加索人群(印度、土耳其和美国)。①GLY71ARG基因型A/A+G/A频率:中国(OR=2.84,95%CI:2.14～3.76),日本(OR=3.22,95%CI:2.03～5.11),马来西亚和泰国人群(OR=2.41,95%CI:1.56～3.72)病例组均显著高于对照组;高加索人群(OR=1.98,95%CI:0.49～8.03)病例组与对照组差异无统计学意义。基因型A/A频率:中国(OR=6.47,95%CI:3.24～12.94),马来西亚和泰国人群(OR=21.01,95%CI:5.21～84.79)病例组均显著高于对照组;日本(OR=3.08,95%CI:1.00～9.49)和高加索人群(OR=5.89,95%CI:0.24～145.49)病例组与对照组差异均无统计学意义。A等位基因频率:中国(OR=2.82,95%CI:2.22～3.58),日本(OR=2.50,95%CI:1.72～3.62),马来西亚和泰国人群(OR=3.01,95%CI:2.07～4.37)病例组均显著高于对照组;高加索人群(OR=2.47,95%CI:0.66～9.25)病例组与对照组差异无统计学意义。②TATA基因型7/7+6/7频率:中国(OR=0.59,95%CI:0.36～0.96)和日本人群(OR=0.15,95%CI:0.04～0.51)对照组均显著高于病例组;马来西亚(OR=1.31,95%CI:0.59～2.92)和高加索人群(OR=1.18,95%CI:0.68～2.02)病例组与对照组差异无统计学意义。基因型7/7频率:中国(OR=1.78,95%CI:0.11～28.69),日本(OR=0.38,95%CI:0.04～3.56),马来西亚(OR=2.46,95%CI:0.46～13.06)和高加索人群(OR=1.45,95%CI:0.91～2.33)病例组与对照组差异均无统计学意义。等位基因7频率:中国(OR=0.65,95%CI:0.35～1.21),马来西亚(OR=1.40,95%CI:0.59～3.29)和高加索人群(OR=1.17,95%CI:0.80～1.69)病例组与对照组差异均无统计学意义;日本人群(OR=0.15,95%CI:0.04～0.50)对照组显著高于病例组。结论现有证据表明UGT1A1基因GLY71ARG多态性与中国、日本、马来西亚及泰国人群新生儿黄疸有关联性;启动子TATA重复多态性与新生儿黄疸无关联性。展开更多
AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastat...AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen. METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC. RESULTS: The distribution of the genotypes was as follows: wild type genotype (WT) (6/6 ) 39.0%, heterozygous genotype (6/7) 49.5%, and homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs 43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the(6/6) when compared to the (6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P =0.08], treatment delays [(6/7, 7/7) vs (6/6); 25.1% vs 19.3%, P = 0.24] or dose reductions [(6/7, 7/7) vs (6/6); 21.5% vs 27.2%, P = 0.07].CONCLUSION: This analysis demonstrates the non-significant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.展开更多
文摘AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen. METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC. RESULTS: The distribution of the genotypes was as follows: wild type genotype (WT) (6/6 ) 39.0%, heterozygous genotype (6/7) 49.5%, and homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs 43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the(6/6) when compared to the (6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P =0.08], treatment delays [(6/7, 7/7) vs (6/6); 25.1% vs 19.3%, P = 0.24] or dose reductions [(6/7, 7/7) vs (6/6); 21.5% vs 27.2%, P = 0.07].CONCLUSION: This analysis demonstrates the non-significant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.
