亚甲基四氢叶酸还原酶A1298C多态性与结直肠癌患者化疗敏感性的相关性研究

The relationship between polymorphism of MTHFR A1298C and chemotherapy sensitivity of colorectal cancer patients

目的探讨结直肠癌(colorectal cancer,CRC)患者亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因A1298C多态性与化疗有效率和预后的相关性。方法收集经病理学确诊的Ⅳ期CRC患者75例,接受标准的FOLFOX6或XELOX方案化疗,化疗前抽取患者外周血,采用DNA测序法检测MTHFR基因A1298C多态性,观察不同基因型化疗有效率和无进展生存时间(PFS),分析二者的相关性。结果 75例CRC者中,MTHFR1298 AA、AC、CC基因型频率分别为61.3%、34.7%、4.0%,化疗有效率分别为39.1%、30.8%、33.3%,差异无统计学意义(P>0.05)。AA型和AC/CC型化疗中位PFS分别为13.3个月、11.4个月,差异具有微弱的边际统计学意义(P=0.068)。结论 MTHFR A1298C基因多态性和患者化疗后有效率无关。MTHFR 1298携带AA基因型的患者化疗后PFS略优于携带C基因型的患者。

Objective To investigate the relationship between the polymorphism of the methylenetetrahydrofolate reduetase （MTHFR） A1298C and the response rate and progression free survival （PFS） of advanced colorectal cancer （CRC） treated by chemotherapy. Methods Seventy-five stage IV CRC patients confirmed by pathology were treated with FOLFOX6 or XELOX regimen and DNA of peripheral blood was obtained before chemotherapy. MTHFR A1298C genotypes were detected by PCR and sequencing method. The response rate and PFS of patients with different genotypes were recorded, relationship between them was analyzed. Results Of the 75 patients, the fl-equencies of MTHFR 1298 AA, AC, CC genotype were 61.3%, 34.7% and 4.0% ; the response rates of AA, AC, CC genotype were 39. 1%, 30.8% , 33.3% , respectively, there was no significant differenee（P 〉0.05）. The mean PFS of AA and AC/CC genotype were 13.3 months and 11.4 months, respectively, there was weak marginal significance （P = 0. 068）. Conclusion The present study indicated that no significant difference between the response rate of chemotherapy and MTHFR A1298C genotype. The PFS of the patients with AA genotype was superior to AC/CC genotype with the weak marginal significance.