二氢嘧啶脱氢酶编码基因DPYD* 5及* 9A突变频率的研究

Study on mutation incidence of DPYD* 5 and* 9A which code dihydropyrimidine dehydrogenase

目的氟尿嘧啶(5-Fu)是各种肿瘤治疗中应用最为广泛的抗肿瘤药物之一。体内80%以上的5-Fu在肝脏内经由二氢嘧啶脱氢酶(DPD)分解代谢。DPYD基因是DPD酶的编码基因,本研究旨在考察DPYD基因的*5及*9A位点在中国汉族乳腺癌患者中的突变频率。方法本研究收集100例乳腺癌患者的外周静脉血,应用基因测序的方法对93例乳腺癌患者DNA标本进行了DPYD*5及*9A位点的测序。结果对于DPYD*5的1627A>G突变位点,有37例发生突变,其中7例为纯合子突变,30例为杂合子突变;对于DPYD*9A的85T>C突变位点,有19例发生突变,其中1例为纯合子突变,18例为杂合子突变。有9例患者呈现DPYD*5/*9A联合突变。结论在中国汉族乳腺癌患者中(93例),DPYD*5的突变频率为39.8%,DPYD*9A的突变频率是20.4%,DPYD*5/*9A联合突变的发生频率为9.7%。

Objective To study the mutation incidence of DPYD ＊ 5 and ＊ 9A coding dihydropyrimidine dehydrogenase（DPD） in Chinese Hun people suffering from breast cancer because DPD catabolizes 5- fluorouracil in liver. Methods Samples of peripheral vein blood were acquired from 100 Chinese Hun people suffering from breast cancer. DPYD ＊ 5 and ＊ 9A were sequenced by gene sequencing of 93 DNA samples. Results Mutation of 1627A 〉 G mutation sites of DPYD ＊ 5 occurred in 37 cases including 7 homozygous mutations, and 30 heterozygous mutations ; Mutation of 85T 〉 C mutation sites of DPYD ＊ 9A occurred in 19 cases, including 1 homozygous mutations and 18 heterozygous mutations. Combined mutations of DPYD ＊ 5 and ＊ 9A were detected in 9 subjects. Conclusions In Chinese Hun people suffering from breast cancer（ n = 93 ）, the mutation rate of DPYD ＊ 5 is 39. 8%, that of DPYD ＊ 9A is 20. 4%. And the combined mutation rate of DPYD ＊ 5 and ＊ 9A is 9. 7%.