DPYD、GSTP1、MTHFR基因多态性对5-FU类基础化疗结直肠癌患者疗效的影响

Effects of DPYD,GSTP1,and MTHFR polymorphisms on clinical outcome of patients with advanced colorectal cancer treated with 5-FU-based chemotherapy

目的探讨二氢嘧啶脱氢酶基因(DPYD)、谷胱甘肽S转移酶P1(GSTP1)和亚甲基四氢叶酸还原酶(MTHFR)与接受以5-FU类为基础的化疗方案治疗的结直肠癌(CRC)患者疗效的关系。方法选择晚期CRC患者90例,其中接受FOLFOX方案34例、接受CapeOX方案56例,化疗至少3周期后评价疗效,应用荧光染色原位杂交测序法检测患者外周血DPYD(rs3918290、rs55886062)、GSTP1(rs1695)、MTHFR(rs1801133、rs1801131)基因型,分析各基因型与CRC患者近期疗效的关系。结果90例CRC患者中,DPYD 2个位点(rs3918290、rs55886062)均为野生型,该样本不符合Hardy-Weinberg遗传平衡检验;携带GSTP1(rs1695)AA、AG+GG基因型的患者化疗后有效率分别为18.9%(17/90)和21.1%(19/90),AG+GG基因型患者化疗失败的可能性是AA型的3.193倍(OR=3.193,95%CI:1.307~7.804,P<0.05);携带MTHFR(rs1801133)CC、TC+TT基因型的患者化疗后有效率分别为6.7%(6/90)和26.7%(24/90),TC+TT基因型患者化疗失败的可能性是CC型的4.000倍(OR=4.000,95%CI:1.431~11.180,P<0.05);携带MTHFR(rs1801131)AA、AC+CC基因型的患者化疗后有效率分别为30.0%(27/90)和10.0%(9/90),二者比较差异无统计学意义(P<0.05)。结论GSTP1(rs1695)及MTHFR(rs1801133)基因多态性与5-FU类药物的疗效有关,而MTHFR(rs1801131)基因多态性与5-FU类药物的疗效无关,检测GSTP1(rs1695)、MTHFR(rs1801133)单核苷酸多态性可以成为预测晚期CRC患者接受以5-FU类为基础的化疗方案疗效的指标。

Objective To investigate the relationship between dihydropyrimidine dehydrogenase(DPYD),glutathione S-transferase P1(GSTP1)and methylenetetrahydrofolate redueta(MTHFR)and the efficacy of 5-FU-based chemotherapy regimens in the treatment of advanced colorectal cancer(CRC).Methods Ninety patients with advanced rectal cancer were selected,including 34 cases receiving FOLFOX regimen and 56 cases receiving CapeOX regimen.After receiving chemotherapy with 5-FU regimen for at least three cycles,the efficacy was evaluated by detecting the genotypes of DPYD(rs3918290,rs55886062),GSTP1(rs1695)and MTHFR(rs1801133,rs1801131)in the peripheral blood.The results were used to analyze the correlation between the genotypes and the efficacy of patients with CRC.Results Among the 90 CRC patients,the genotypes of DPYD(rs3918290,rs55886062)were all wild type,which did not meet the Hardy-Weinberg genetic balance test.The effective rate of patients with GSTP1(rs1695)AA,AG+GG genotypes after chemotherapy was 18.9%(17/90)and 21.1%(19/90),and patients with AG+GG genotype were 3.193 times more likely to fail chemotherapy than those with AA genotype(OR=3.193,95%CI:1.307-7.804,P<0.05);the effective rates of patients with MTHFR(rs1801133)CC and TC+TT genotypes after chemotherapy were 6.7%(6/90)and 24.7%(24/90),and patients with TC+TT genotype were 4.000 times more likely to fail chemotherapy than those with CC genotype(OR=4.000,95%CI:1.431-11.180,P<0.05).The effective rates of patients with MTHFR(rs1801131)AA,AC+CC genotypes after chemotherapy were 30.0%(27/90)and 10.0%(9/90).There was no significant difference between the two groups(P<0.05).Conclusions GSTP1(rs1695)and MTHFR(rs1801133)gene polymorphisms may be associated with clinical outcome of 5-FU-based chemotherapy in patients with advanced CRC,and MTHFR(rs1801131)gene polymorphism is not correlated with the efficacy of 5-FU-based chemotherapy.Therefore,detecting the single nucleotide polymorphisms of GSTP1(rs1695)and MTHFR(rs1801133)may predict the efficacy of 5-FU-based chemotherapy for patients with advanced CRC.