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

WANG Yong; XU Xi; WANG Hui

doi:10.3969/j.issn.1002-266X.2014.41.007

Abstract：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.