结直肠癌患者DPYD基因多态性与5-FU毒性反应相关的Meta分析  

Influence of DPYD genetic polymorphisms on 5-Fluorouracil toxicities in patients with colorectal cancer:a Meta-analysis

作　　者：王勇[1] 徐曦[1] 王慧[1] 

机构地区：[1]沈阳医学院附属沈洲医院,沈阳110002

出　　处：《山东医药》2014年第41期18-21,共4页Shandong Medical Journal

摘　　要：目的探讨结直肠癌患者二氢嘧啶脱氢酶（DPYD）基因多态性与5-氟尿嘧啶（5-FU）代谢及化疗后毒性反应的关系。方法参照Cochrance协作网制定的检索策略进行检索,电子数据库包括：MEDLINE（1966~2013）,the Cochrane Library Database（Issue 12,2013）,EMBASE（1980~2013）,CINAHL（1982~2013）,Web of Science（1945~2013）,中国生物医学文献数据库（1982~2013）,万方（1998~2013）和中国知网（1915~2013）。Meta分析采用Stata 12.0（Stata Corp,College Station,TX,USA）统计软件进行。结果本Meta分析共计纳入7项队列研究,包括946例结直肠癌患者。DPYD基因多态性与结直肠癌患者的骨髓抑制高发生率、胃肠道反应和手足综合征显著相关（P均〈0.05）。根据DPYD基因多态位点的不同进行亚组分析发现,IVS14＋1、464T〉A和2194G〉A多态性与接受5-FU化疗的结直肠癌患者骨髓抑制发生率显著相关（P均〈0.05）。IVS14＋1、496A〉G和2194G〉A多态性与胃肠道反应的发生率相关（P均〈0.05）。进一步根据种族不同进行亚组分析结果表明,DPYD基因多态性可能与亚洲人群骨髓抑制和胃肠道反应有关（P均〈0.05）,但在欧洲人群中并没有此现象发生（P〉0.05）。结论DPYD基因多态性可能与亚洲人群中结直肠癌患者体内5-FU化疗后毒性反应有关。Objective To comprehensively investigate the correlations between genetic polymorphisms in dihydropyrimidine dehydrogenase（DPYD） gene and 5-fluorouracil（5-FU） toxicities in patients with colorectal cancer（CRC）.Methods Articele were retrieved according to search strategy made by cochrance web.Electronic database included The MEDLINE（1966-2013）,the Cochrane Library Database（Issue 12,2013）,EMBASE（1980-2013）,CINAHL（1982-2013）,Web of Science（1945-2013）,the Chinese Biomedical Database（CBM）（1982-2013）,Wanfang（1998-2013） and CNKI（1915-2013）.Meta-analyses were conducted with the use of STATA software（Version 12.0,Stata Corporation,College Station,Texas USA）.Results Seven clinical cohort studies with a total of 946 CRC patients met our inclusion criteria.Our findings showed that DPYD genetic polymorphisms were significantly correlated with high incidences of marrow suppression,gastrointestinal reaction and hand-foot syndrome in CRC patients.SNP-stratified analysis indicated that there were remarkable connections of IVS14 ＋ 1,464 T〉 A,and 2194 G 〉A polymorphisms with the incidence of marrow suppression in CRC patients receiving 5-FU chemotherapy（all P〈0.05）.Furthermore,we found that IVS14 ＋ 1,496 A 〉G and 2194 G 〉A polymorphisms were correlated with the incidence of gastrointestinal reaction（all P〈0.05）.Ethnicity-stratified analysis also revealed that DPYD genetic polymorphisms might contribute to the development of marrow suppression and gastrointestinal reaction among Asians（all P〈0.05）,but not among Caucasians（all P〉0.05）.Conclusion DPYD genetic polymorphisms may be correlated with the incidence of 5-FU toxicities in Asians with CRC.

关 键 词：结直肠肿瘤 二氢嘧啶脱氢酶 基因多态性 5-氟尿嘧啶 META分析 

分 类 号：R735.3[医药卫生—肿瘤]