亚甲基四氢叶酸还原酶基因多态性与胃癌化疗的敏感性关系的研究

高长明; 陆建伟; Takezaki Toshiro; 吴建中; 曹海霞; 陈环球; 冯继锋; Tajima Kazuo

Abstract

高长明,陆建伟,Takezaki Toshiro,吴建中,曹海霞,陈环球,冯继锋,Tajima Kazuo.亚甲基四氢叶酸还原酶基因多态性与胃癌化疗的敏感性关系的研究[J].Chinese journal of Epidemiology,2004,25(12):1054-1058

亚甲基四氢叶酸还原酶基因多态性与胃癌化疗的敏感性关系的研究

Polymorphism of methylenetetrahydrofolate reductase and sensitivity of stomach cancer to fluoropyrimidinebased chemotherapy

Received:November 19, 2003 Revised:November 19, 2003

DOI：

KeyWord: 胃肿瘤亚甲基四氢叶酸还原酶化学治疗基因型

English Key Word: Stomach neoplasms Methylenetetrahydrofolate reductase Chemotherapy Genotypes

FundProject:江苏省科技厅社会发展科学基金资助项目(BS2003048)日本文科省国际学术研究癌症特别研究经费资助项目(08042015)

Author Name	Affiliation
GAO Chang-ming	Department of Epidemiology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, China
LU Jian-wei	Department of Epidemiology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, China
Takezaki Toshiro	日本爱知县研究所疫学、预防部
WU Jian-zhong	Department of Epidemiology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, China
CAO Hai-xia	Department of Epidemiology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, China
CHEN Huan-qiu	Department of Epidemiology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, China
FENG Ji-feng	Department of Epidemiology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, China
Tajima Kazuo	Department of Epidemiology, Jiangsu Province Cancer Institute and Hospital, Nanjing 210009, China

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Abstract:

目的研究亚甲基四氢叶酸还原酶(MTHFR) 因C677T、A1298C多态与胃癌患者对5-FU为基础的化疗敏感性和毒性的关系。方法收集经病理学确诊的晚期胃癌患者75例,病例化疗前均抽静脉血,提取白细胞DNA,用聚合酶链反应-限定性片段长度多态性技术检测MTHFR基因型。所有患者经5-FU为基础的化疗方案治疗。结果 (1)在75例晚期胃癌患者中,MTHFR C677TC／C、C／T、T／T基因型者分别为24例(32.0%)、33例(44.0%)和18例(24.0%) MTHFR A1298CA／A、A／C、C／C基因型者分别为52例(69.3%)、22例(29.3%)和1例(1.3%) 经化疗后22例患者有效,总有效率29.3%。(2)MTHFR C677T T／T基因型者化疗的有效率为83.3%,显著高于T／C基因型者(15.2%,x2=22.27,P=0.000)和C／C基因型者(8 3%,x2=23.44,P=0.000)。C677T T／T基因型患者化疗敏感性是携带C677T C等位基因者的7.64倍(调整了性别、年龄、以往辅助化疗史及化疗方案,95%CI:3.14-18.62)。MTHFR A1298C A／A基因型者的有效率(36.5%),显著高于携带A1298C C(13.0%)等位基因者(x2=4 19,P=0.041 调整OR=3 75,95%CI:0.94-14.87)。同时携带MTHFR C677T T／T基因型和A1298C A／A基因型者化疗的有效率(86.7%)显著高于其他基因型者(15.0%,Fisher's exact:P=0.000,调整OR=6.57.95

English Abstract:

Objective To investigate the relationship between polymorphisms of the methylenetetrahydrotolate reductase ( M'1、 Hr'R ) 1;b771~ or A1298C and the response to iluoropyrimidine(5-FU)-based chemotherapy in advanced stomach cancer (SC).Methods 75 cases with advanced SC were analyzed. All patients were treated with S-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. MTHFR genotypes were detected by PCR-RFLP method. Results (1) Of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 32.0%，44.0% and 24.0%，while the frequencies of MTHFR A1298C Af A, A/C and C/C genotype were 69. 3 %，29.3% and 1 .3%，respectively. The overal response rate to S-FU-based chemotherapy was 29.3%.( 2 ) The response rate to therapy among MTHFR C677T T/T genotype patients ( 83 .3%)was significantly higherthan the C677T C/T genotype (15 . 2 %, xZ=22. 27, P二0.000) or the C677T C/C genotype (8.3%.x‘二23.44,P=0.000).As compared with patients with C677T C allele, patients with C677T T/T genotype had a 7.64-fold sensitivity to S-FU-based chemotherapy (adjusted for sex, age, prior adjuvant therapy and chemotherapy program, 95 % Cl: 3.14- 18. 62).The response rate to therapy among patients with MTHFR A1298CA genotype ( 36. 5 %)was significantly higher than patients with A1298C C allele(13.0%，=4.19,P一0.041,adjusted OR一3.75,950,6 C1:0.94-14.87)·The response rate to therapy among patients with MTHFR C677T T/T and A1298C州A genotypes (86.70.6)was significantly higher than other groups of C677T and A1298C genotypes(15.0%，Fisher exact: P=0.000, adjusted OR=6.57,95 % C1:2.8-15.6).(3) The incidence rates of nausea/vomiting in MTHFR C677T T/T, C/T or A1298C习A genotypes were significantly higher than other genotypes, but the incidence rates of other treatment related adverse reaction in MTHFR C677T or A1298C genotypes were not significantly different. Conclusions These results in the present study suggested that the polymorphisms of MTHFR were associated with clinical response to S-FU-based chemotherapy, suggesting that MTHFR genotypes could identify advanced SC patients that would be responsive to S-FU-based chemotherapy.

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