title: CCND1 G870A polymorphism is associated with toxicity of methotrexate in childhood acute lymphoblastic leukemia.
abstract: CCND1 plays a key role in cell cycle progression and may cause methotrexate (MTX) resistance, as well as its cytotoxicity. CCND1 870A variant allele is associated with altered transcripts of this gene. We hypothesized that this polymorphism may contribute to the elimination rate and hepatotoxicity of MTX in childhood acute lymphoblastic leukemia (ALL). We genotyped the CCND1 G870A polymorphism in 125 childhood ALL patients treated with HDMTX. We found no notable associations between G870A polymorphism and the risk of delayed MTX elimination. However, this polymorphism was significantly associated with an increased risk of MTX hepatotoxicity [adjusted odds ratio (OR) = 4.44, 95% confidence interval (CI) = 1.35-14.63 for AG versus GG and adjusted OR = 6.39, 95% CI = 1.82-22.43 for AA versus GG]. Our results indicated that the CCND1 G870A polymorphism may be involved in the hepatotoxicity of MTX and act as a biological marker.
authors.affiliation: Department of Hematology and Oncology, The Affiliated Nanjing Children's Hospital of Nanjing Medical University Nanjing 210008, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Hematology and Oncology, The Affiliated Nanjing Children's Hospital of Nanjing Medical University Nanjing 210008, China.
authors.forename: Liucheng
authors.initials: L
authors.lastname: Rong
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University Nanjing 210029, China.
authors.forename: Na
authors.initials: N
authors.lastname: Tong
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University Nanjing 210029, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University Nanjing 210029, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Oncology, The Affiliated Nanjing Children's Hospital of Nanjing Medical University Nanjing 210008, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D019938:Cyclin D1 / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005838:Genotype; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D009154:Mutation; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
chemical_list: C530104:CCND1 protein, human; D019938:Cyclin D1; D008727:Methotrexate
keywords: CCND1; MTX toxicity; childhood acute lymphoblastic leukemia; polymorphism