title: Homozygous CDA*3 is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patients.
abstract: Among 242 Japanese pancreatic cancer patients, three patients (1.2%) encountered life-threatening toxicities, including myelosuppression, after gemcitabine-based chemotherapies. Two of them carried homozygous CDA*3 (CDA208G>A [Ala70Thr]), and showed extremely low plasma cytidine deaminase activity and gemcitabine clearance. Our results suggest that homozygous *3 is a major factor causing gemcitabine-mediated severe adverse reactions among the Japanese population.
authors.affiliation: Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. hiueno@ncc.go.jp
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.forename: N
authors.initials: N
authors.lastname: Kaniwa
authors.forename: T
authors.initials: T
authors.lastname: Okusaka
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: C
authors.initials: C
authors.lastname: Morizane
authors.forename: S
authors.initials: S
authors.lastname: Kondo
authors.forename: E
authors.initials: E
authors.lastname: Sugiyama
authors.forename: S R
authors.initials: SR
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Hasegawa
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: N
authors.initials: N
authors.lastname: Saijo
authors.forename: J
authors.initials: J
authors.lastname: Sawada
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D003564:Cytidine Deaminase / Q000235:genetics*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D020641:Polymorphism, Single Nucleotide; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D003564:Cytidine Deaminase; D000093542:Gemcitabine