摘要
目的伊立替康（CPT-11）联合5-氟尿嘧啶/亚叶酸钙（5-FU/LV）治疗转移性结直肠癌疗效优于5-FU／LV，但CPT-11的毒副作用不可预测。尿苷二磷酸葡糖苷酸转移酶1A1（uridine diphosphate glucuronide transferase 1A1,UGT1A1）是参与CPT11在人体内失活代谢最重要的酶，其酶活性受到UGT1A1基因多态性的调控。亚洲人群晚期结直肠癌UGT1A1＊28和UGT1A1＊6基因多态性与CPT11相关毒性存在关系，但结论并不一致。本研究采用Meta分析的方法研究亚洲人群晚期结直肠癌UGT1A1＊28基因多态性和UGT1A1＊6基因多态性与CPT-11相关毒性之间的关系。方法检索PubMed、Embase、Cochrane图书馆、中国生物文献数据库、重庆维普数据库、中国期刊全文数据库和万方数据库中2014-12之前发表的相关文献，以CPT11、UGT1A1、多态性和结直肠癌为检索词，按纳入标准，选择相关的文献，提取数据后，采用RevMan 5．2及R软件计算合并的OR值及其95％CI，并对其发表偏倚进行评价。结果共纳入10篇文献，在亚洲人群晚期结直肠癌中，UGT1A1＊28／＊28（OR=3．58，95％CI为1．91～6．71，P〈0．001）和UGT1A1＊1/＊28（OR=1．82，95％CI为1．30～2．54，P=0．0004）较UGT1A1＊1／＊1发生3～4级中性粒细胞减少的风险增加；UGT1A1＊28／＊28（OR=5．51，95％CI为2．82～10．75，P〈0．001）和UGT1A1＊1／＊28（OR-1．83，95％CI为1.22～2．76，P=0．004）较UGT1A1＊1/＊1发生3～4级腹泻的风险增加；UGT1A1A/A较UGT1A1G/G发生3～4级中性粒细胞减少的风险增加，OR=2．4l，95％CI为1．28～4．55，P=0．007；UGT1A1G/A较UGT1A1G／G不会增加3～4级中性粒细胞减少的风险，OR=1．32，95％CI为0．96～1．83，P=0．09；UGT1A1A／A（OR=4．40，95％CI为2．12～9．12，P〈0．001）和UGT1A1G／A（OR-1．89，95％CI为1．26～2．84，P=0．002）较UGT1A1G/G发生3～4级腹泻的风险增加。结论在亚洲人群晚期结直肠�
OBJECTIVE Irinotecan （IRI）-based combination therapy is more effective compared with 5 fluorouracil （5-FU）/leucovorin alone. However, its use is accompanied by a comparably high incidence of unpredictable severe toxici ty. The uridine diphosphate glucuronosyltransferase （UGT） 1A1 is an essential enzyme involved in the complex melabo lism of IRI, and its activity is regulated by UGTIA1 polymorphisms. Researchers have investigated the effect of UGT1A1 ＊ 28 and UGT1A1 ＊ 6 on the IRI-induced toxicities in Asians with colorectal cancer （CRC）. However, results are both conflicting and difficult to interpret. This meta-analysis in Asians was conducted to investigate the possible asso ciation of uridine diphosphate glucuronosyltransferase （UGT） 1A1 gene polymorphisms with irinotecan （IRI） induced toxic reactions in colorectal cancer （CRC）. METHODS We searched PubMed,Embase,CNKI, et al until Dec 2014 to identify eligible studies, as CPT-11, UGT1A1, polymorphism and eolorectal cancer were key words, extracted data, assessed methodological quality,performed statistical analysis using REVMAN 5.2 and R software and assessed the pooled ORs with 95%CI. Publication bias was evaluated at the same time. RESULTS Ten trials were included. The risk of grade 3-4 neutropenia was higher in patients with UGTIA1 ＊ 28/＊ 28 genotype or UGTIA1 ＊ 1/＊ 28 genotype than in those with UGT1A1 ＊1/＊1 genotype（OR= 3.58,95%CI：1.91-6.71,P〈0. 001; OR=1. 82,95%CI：1.30-2.54,P= 0. 000 4; respectively）. The risk of grade 3-4 diarrhea was higher in patients with UGT1A1 ＊ 28/＊ 28 genotype or UGTIA1 ＊ 1/＊ 28 genotype than in those with UGT1A1 ＊ 1/＊ 1 genotype（OR= 5.51,95%CI： 2. 82-10. 75, P〈0. 001; OR=1.83,95%CI：1. 22-2.76,P=0.004; respectively）. The risk of grade 3-4 diarrhea was higher in patients with UGT1A1A/A genotype or UGTIA1G/A genotype than in those with UGTIAIG/G genotype （OR= 4. 40, 95% CI： 2.12-9.12,P〈0. 001; OR=1. 89,95%CI： 1.26-2.84,P=0. 002; respectively）. The
出处
《中华肿瘤防治杂志》
CAS
北大核心
2015年第20期1634-1640,共7页
Chinese Journal of Cancer Prevention and Treatment
