title: Influences of ERCC1, ERCC2, XRCC1, GSTP1, GSTT1, and MTHFR polymorphisms on clinical outcomes in gastric cancer patients treated with EOF chemotherapy.
abstract: This study investigated the associations between genetic polymorphisms of six genes involved in DNA repair, detoxification pathways, and fluoropyrimidine metabolism and clinical outcomes in MGC patients receiving EOF treatment. This retrospective study included 108 Chinese MGC patients receiving EOF as first-line chemotherapy. Nine single nucleotide polymorphisms (SNPs) of six genes (ERCC1 rs2298881, ERCC2 rs13181 and rs1799793, XRCC1 rs25487 and rs25489, GSTP1 rs1695, GSTT1 rs2266637, and MTHFR rs1801133 and rs1801131) were genotyped, and the associations between each SNP and clinical outcome were analyzed. XRCC1 rs25487 A allele was significantly associated with progression disease (PD) to EOF (p = 0.002), and patients with AA genotype had significantly poorer progression-free survival (PFS) (p = 0.001) and overall survival (OS) (p = 0.041) compared with patients with the G allele (GG + GA). ERCC2 rs13181 G allele was significantly associated with PD (p = 0.026), and G carriers (GG + GT) tended to have poorer PFS (p = 0.092) than TT homozygotes. ERCC2 rs1799793 GA genotype was associated with unfavorable PFS (p = 0.034) and a tendency toward poorer OS (p = 0.090) compared with GG homozygotes. Patients were categorized as either good (0 risk factors) or poor risk (≥1 unfavorable SNPs) using a prognostic index based on XRCC1 rs25487 AA, ERCC2 rs13181 (GG + GT), and ERCC2 rs1799793 GA genotypes, with median OS and PFS of 534 days, 281 days (p = 0.009) and 206 days, and 123 days (p < 0.001), respectively. These results suggest that the prognostic index comprising XRCC1 rs25487, ERCC2 rs13181, and rs1799793 polymorphisms may be a useful predictor of clinical outcomes in MGC treated with EOF.
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China.
authors: Rujiao
authors: R
authors: Liu
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China.
authors: Xiaoying
authors: X
authors: Zhao
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China.
authors: Xin
authors: X
authors: Liu
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China.
authors: Zhiyu
authors: Z
authors: Chen
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China.
authors: Lixin
authors: L
authors: Qiu
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China.
authors: Ruixuan
authors: R
authors: Geng
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China.
authors: Weijian
authors: W
authors: Guo
authors: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.|Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China.
authors: Guang
authors: G
authors: He
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China.
authors: Jiliang
authors: J
authors: Yin
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China.
authors: Jin
authors: J
authors: Li
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. xddr001@163.com.|Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, People's Republic of China. xddr001@163.com.
authors: Xiaodong
authors: X
authors: Zhu
mesh_terms: D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics*; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D056726:Genetic Association Studies / Q000379:methods; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D015251:Epirubicin; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D005472:Fluorouracil
keywords: EOF5 chemotherapy; Gastric cancer; Overall survival; Progression-free survival; SNP polymorphism