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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.

medical oncology

Association of single nucleotide polymorphisms in MTHFR and ABCG2 with the different efficacy of first-line chemotherapy in metastatic colorectal cancer