Li Qiang, Liu Ying, Zhang Hong-Mei, Huang Yin-Peng, Wang Tian-Yi, Li Dong-Sheng, Sun Hong-Zhi
Department of Oncology, Jining No. 1 People's Hospital, No. 6 Jiankang Road, Jining, Shandong 272011, China.
Department of Immunology, Laiwu Municipal Center for Disease Control & Prevention, Laiwu 271100, China.
Gastroenterol Res Pract. 2014;2014:827989. doi: 10.1155/2014/827989. Epub 2014 Dec 28.
Our meta-analysis aggregated existing results from relevant studies 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). The MEDLINE (1966∼2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980∼2013), CINAHL (1982∼2013), Web of Science (1945∼2013), and the Chinese Biomedical Database (CBM) (1982∼2013) were searched without language restrictions. Meta-analyses were conducted with the use of STATA software (Version 12.0, Stata Corporation, College Station, TX, USA). Seven clinical cohort studies with a total of 946 CRC patients met our inclusion criteria, and NOS scores of each of the included studies were ≥5. Our findings showed that DPYD genetic polymorphisms were significantly correlated with high incidences of 5-FU-related toxicity in CRC patients. SNP-stratified analysis indicated that there were remarkable connections of IVS14+1G>A, 464T>A, and 2194G>A polymorphisms with the incidence of marrow suppression in CRC patients receiving 5-FU chemotherapy. Furthermore, we found that IVS14+1G>A, 496A>G, and 2194G>A polymorphisms were correlated with the incidence of gastrointestinal reaction. Ethnicity-stratified analysis also revealed that DPYD genetic polymorphisms might contribute to the development of marrow suppression and gastrointestinal reaction among Asians, but not among Caucasians. The present meta-analysis suggests that DPYD genetic polymorphisms may be correlated with the incidence of 5-FU-related toxicity in CRC patients.
我们的荟萃分析汇总了相关研究的现有结果，以全面调查二氢嘧啶脱氢酶（DPYD）基因中的基因多态性与结直肠癌（CRC）患者中5-氟尿嘧啶（5-FU）毒性之间的相关性。对MEDLINE（1966年至2013年）、Cochrane图书馆数据库（2013年第12期）、EMBASE（1980年至2013年）、CINAHL（1982年至2013年）、科学引文索引（1945年至2013年）以及中国生物医学数据库（CBM）（1982年至2013年）进行了检索，无语言限制。使用STATA软件（版本12.0，美国德克萨斯州大学站Stata公司）进行荟萃分析。七项临床队列研究共纳入946例CRC患者，符合我们的纳入标准，且每项纳入研究的NOS评分均≥5。我们的研究结果表明，DPYD基因多态性与CRC患者中5-FU相关毒性的高发生率显著相关。单核苷酸多态性分层分析表明，IVS14 + 1G>A、464T>A和2194G>A多态性与接受5-FU化疗的CRC患者骨髓抑制的发生率有显著关联。此外，我们发现IVS14 + 1G>A、496A>G和2194G>A多态性与胃肠道反应的发生率相关。种族分层分析还显示，DPYD基因多态性可能导致亚洲人而非白种人发生骨髓抑制和胃肠道反应。本荟萃分析表明，DPYD基因多态性可能与CRC患者中5-FU相关毒性的发生率相关。
