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

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 dihydropyri-midine 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, 464T >A, and 2194G >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, 496A >G and 2194G >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).Conclu-sion DPYD genetic polymorphisms may be correlated with the incidence of 5-FU toxicities in Asians with CRC.