title: Association of single nucleotide polymorphisms in MTHFR and ABCG2 with the different efficacy of first-line chemotherapy in metastatic colorectal cancer.
abstract: Either oxaliplatin- or irinotecan-containing regimen could receive a good effectiveness in patients with metastatic colorectal cancer as the first-line chemotherapy, but not all patients would benefit from the treatment they have received. This study was to investigate the role of single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) and ATP-binding cassette sub-family G member 2 (ABCG2) in selecting the most appropriate treatment for individual patients. Ninety-two metastatic colorectal cancer patients treated with first-line 5-fluoropyrimidine (5-FU), leucovorin, and oxaliplatin (FOLFOX), capecitabine, and oxaliplatin (XELOX) and sixty-two patients receiving 5-FU, leucovorin, and irinotecan (FOLFIRI) were reviewed. The SNPs of MTHFR and ABCG2 were detected using gene sequencing method after DNA PCR amplification, which was extracted from peripheral blood karyocytes. Clinical characteristics and gene polymorphisms were evaluated in univariate and multivariate analysis as predictive factors for response rate (RR) and progression-free survival (PFS). In patients bearing 2-4 genotypes of MTHFR 677C/C, MTHFR 1298 A/C or C/C, ABCG2 34G/G, and ABCG2 421C/A or A/A, those who received oxaliplatin-based chemotherapy achieved a higher RR (41.7 vs. 18.8 %, P = 0.027) and longer median PFS (mPFS) than irinotecan-based therapy [8.9 vs. 7.1 m, FOLFIRI: hazard ratio (HR) = 1.722, 95 % confidence interval (CI) 1.026-2.892, P = 0.040, compared with FOLFOX/XELOX]; on the contrary, patients carrying 0 or 1 above genotype exhibited better outcomes after receiving FOLFIRI chemotherapy (mPFS: 9.3 vs. 6.4 m, FOLFIRI: HR = 0.422, 95 % CI 0.205-0.870, P = 0.019, compared with FOLFOX/XELOX). Combination of SNPs with MTHFR and ABCG2 may play a role in helping clinicians to select first-line chemotherapy for patients with metastatic colorectal cancer.
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors: Jing
authors: J
authors: Zhao
authors: Wenhua
authors: W
authors: Li
authors: Dan
authors: D
authors: Zhu
authors: Qihe
authors: Q
authors: Yu
authors: Zhe
authors: Z
authors: Zhang
authors: Menghong
authors: M
authors: Sun
authors: Sanjun
authors: S
authors: Cai
authors: Wen
authors: W
authors: Zhang
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010071:Oxaloacetates; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012189:Retrospective Studies
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D003841:Deoxycytidine; D000069287:Capecitabine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin