title: DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia.
abstract: We aimed to investigate the association between dihydropyrimidine dehydrogenase (DPYD) gene polymorphisms and the risk of pediatric acute lymphoblastic leukemia (ALL) and its prognosis after chemotherapy. A total of 147 pediatric ALL patients diagnosed by our hospital between January 2011 and December 2014 were included in the case group, and 102 healthy people who received a physical examination during the same time frame in our hospital were included in the control group. DNA sequencing was applied for site determination and genotyping of the DPYD 85T > C, 2194G > A, 1156G > T, and IVS14 + 1G > A polymorphisms. The genotype and allele frequencies of the two groups were compared. A significant difference was found in the comparison of the mutant gene and allele frequencies of the 85T > C polymorphism between the case and control groups (P < 0.05). The CT and CC genotypes in the 85T > C polymorphism were associated with the risk of the disease (OR = 1.592, 95 % CI = 1.010-2.509), suggesting that the recessive gene (85C) was more likely to lead to the occurrence of ALL compared with the dominant gene (85T) (P < 0.05). Patients carrying the C allele of the 85T > C polymorphism presented higher damage of their liver functions and higher infection rates compared with patients carrying the non-C allele (P < 0.05). A higher proportion of liver function damage and a higher infection rate were found in patients with the GA genotype in the IVS14 + 1G > A polymorphism compared with the GG genotype (P < 0.05). The complete remission (CR) rate in patients with the GG genotype in the IVS14 + 1G > A polymorphism was higher than in patients with the GA genotype (P = 0.020). After 5-fluorouracil/calcium folinate (5-FU/CF)-based chemotherapy, the event-free survival (EFS) rate of patients with the TT genotype was higher than patients with the CT and CC genotypes (P < 0.05). Our results revealed that the C allele of the 85T > C polymorphism might be associated with susceptibility to pediatric ALL. Patients carrying the C allele may have an increased risk of ALL. Thus, the 85T > C polymorphism may be a predictor of CR for pediatric ALL patients.
authors: Department of Hematology, First Affiliated Hospital to Zhengzhou University, Jianshe East Road, No. 1, Two Seven District, Zhengzhou, 450052, Henan, People's Republic of China.|Department of Hematology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, Henan, People's Republic of China.
authors: Xiao-Qiang
authors: XQ
authors: Zhao
authors: Department of Hematology, First Affiliated Hospital to Zhengzhou University, Jianshe East Road, No. 1, Two Seven District, Zhengzhou, 450052, Henan, People's Republic of China.
authors: Wei-Jie
authors: WJ
authors: Cao
authors: Department of Hematology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, Henan, People's Republic of China.
authors: Hai-Ping
authors: HP
authors: Yang
authors: Department of Hematology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, Henan, People's Republic of China.
authors: Xue-Wen
authors: XW
authors: Yang
authors: Department of Hematology, First Affiliated Hospital to Zhengzhou University, Jianshe East Road, No. 1, Two Seven District, Zhengzhou, 450052, Henan, People's Republic of China.
authors: Ping
authors: P
authors: Tang
authors: Department of Hematology, First Affiliated Hospital to Zhengzhou University, Jianshe East Road, No. 1, Two Seven District, Zhengzhou, 450052, Henan, People's Republic of China. sunling12231@163.com.
authors: Ling
authors: L
authors: Sun
authors: Department of Hematology, First Affiliated Hospital to Zhengzhou University, Jianshe East Road, No. 1, Two Seven District, Zhengzhou, 450052, Henan, People's Republic of China. gaoxing10301@163.com.
authors: Xing
authors: X
authors: Gao
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D012307:Risk Factors
chemical_list: D042943:Dihydrouracil Dehydrogenase (NADP); D002955:Leucovorin; D005472:Fluorouracil
keywords: 1156G > T; 2194G > A; 5-Fluorouracil; 85T > C; Acute lymphoblastic leukemia; DPYD gene polymorphism; VS14 + 1G > A