title: ABCC2-24C > T polymorphism is associated with the response to platinum/5-Fu-based neoadjuvant chemotherapy and better clinical outcomes in advanced gastric cancer patients.
abstract: Several studies have evaluated the efficacy of neoadjuvant treatment using oxaliplatin and fluoropyrimidines in advanced gastric cancer (GC). However, preoperative biomarkers predictive of clinical outcome remain lacking. We examined polymorphisms in the MTHFR, DPYD, UMPS, ABCB1, ABCC2, GSTP1, ERCC1, and XRCC1 genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 103 GC patients treated with preoperative chemotherapy. DNA was extracted from peripheral blood cells, and the genotypes were analyzed using a SNaPShotTM assay, polymerase chain reaction amplification, and sequencing. The ABCC2-24C > T (rs717620) genotype was associated with pathologic response to neoadjuvant chemotherapy. Patients with the TT and TC genotypes responded to neoadjuvant chemotherapy 3.80 times more often than those with the CC genotype (95% CI: 1.27-11.32). Patients with the CC genotype also had poorer outcomes than those with other genotypes. Thus, ABCC2-24C > T polymorphism may help to predict the response to preoperative chemotherapy in GC patients.
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Shan
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Aitang
authors.initials: A
authors.lastname: Xiao
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Zhaodong
authors.initials: Z
authors.lastname: Xing
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Xue
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Zhemin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Tissue Bank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Rulin
authors.initials: R
authors.lastname: Miao
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Lianhai
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Zhaode
authors.initials: Z
authors.lastname: Bu
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Aiwen
authors.initials: A
authors.lastname: Wu
authors.affiliation: Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.|Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.|Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020360:Neoadjuvant Therapy; D010984:Platinum / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics
chemical_list: D005472:Fluorouracil; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010984:Platinum; C000715087:ABCC2 protein, human
keywords: ABCC2; gastric cancer; neoadjuvant chemotherapy; overall survival; rs717620