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.
Highlights
Colorectal cancer (CRC) is one of the commonly diagnosed cancers among patients, which ranks the third for males and the second for females worldwide
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
We detected the SNPs in MTHFR 677C[T, 1298A[C, ABCG2 34G[A, and 421C[A in patients with metastatic colorectal cancer (mCRC) who had received FOLFOX/XELOX or FOLFIRI as first-line chemotherapy, and combined with the clinical features, we investigated the potential markers for selecting the first-line chemotherapy
Summary
Colorectal cancer (CRC) is one of the commonly diagnosed cancers among patients, which ranks the third for males and the second for females worldwide. Systemic combination chemotherapy is the mainstay of the treatment for patients with metastatic colorectal cancer (mCRC). Treatment for patients with mCRC has evolved significantly over the last 10 years with the use of new active cytotoxic agents, including oxaliplatin and irinotecan plus targeted monoclonal antibodies bevacizumab, cetuximab, and panitumumab; 5-fluoropyrimidine (5-FU), 802 Page 2 of 7. Med Oncol (2014) 31:802 leucovorin (CF), and oxaliplatin (FOLFOX), capecitabine, and oxaliplatin (XELOX) or 5-FU, CF, and irinotecan (FOLFIRI) are the standard chemotherapy treatment for metastatic colorectal cancer in practice with equivalent treatment effectiveness [2,3,4]. It is of great importance to identify biomarkers that could help select the optimum regimen for each patient
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