640 - The predictive role of MTHFR and ABCG2 single nucleotide polymorphisms on the outcome of advanced colorectal cancer treated with first-line chemothe...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Jing Zhao
Authors J. Zhao1, W. Zhang1, W. Li1, J. Li1, W. Guo1, S. Cai2, M. Sun1, Z. Zhang1, D. Zhu1, Q. Yu1
  • 1Department Of Medical Oncology, Fudan University Shanghai Cancer Center, 200032 - Shanghai/CN
  • 2Colorectal Surgery Department, Fudan University Shanghai Cancer Center, 200032 - Shanghai/CN

Abstract

Objective

Chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX or XELOX) or irinotecan (FOLFIRI) has become the mainstay of treatment for advanced colorectal cancer. Since not all patients would benefit from the chemotherapy they received, exploring factors that would predict better effectiveness remains meaningful for understanding the concept of individual treatment. The purpose of this study is to confirm the predictive role of a serial of SNPs, MTHFR C677T, A1298C, ABCG2 G34A and C421A, as well as the clinical features for the efficacy of first-line chemotherapy in advanced colorectal cancer.

Methods

Patients with advanced colorectal cancer and treated with first-line standard FOLFOX/XELOX or FOLFIRI regimens between January 2009 and May 2011 at Fudan University Shanghai Cancer Center were retrospectively studied. Gene polymorphisms of MTHFR and ABCG2 were detected using gene sequencing method, after DNA extraction from peripheral blood karyocytes and PCR amplification.

Results

Of all 154 patients, patients with 3 ∼ 4 of the favorable genotypes (MTHFR 677C/C, MTHFR 1298 A/A, ABCG2 G/A or A/A, and ABCG2 421C/A or A/A) had a longer PFS than those with 0 ∼ 2 above genotypes (9.8m vs. 7.5m, P = 0.013; HR = 0.627, 95%CI: 0.427 ∼ 0.920, P = 0.017) The radical resection of primary lesion was also found as an independent factor for both PFS (HR = 0.524, 95%CI: 0.320 ∼ 0.859, P = 0.010) and OS (HR = 0.291, 95%CI: 0.147 ∼ 0.575, P = 0.000). Interestingly, stratified univariate analysis revealed that patients with 2 ∼ 4 genotypes of MTHFR 677C/C、MTHFR 1298 A/C or C/C、ABCG2 34G/G and ABCG2 421C/A or A/A would benefit more from FOLFOX/XELOX than FOLFIRI as first-line chemotherapy (FOLFIRI: HR = 1.722, 95%CI: 1.026 ∼ 2.892, P = 0.040, compared with FOLFOX/XELOX). In contrast, patients with 0 or 1 above-mentioned genotype would have better outcomes if receiving FOLFIRI (FOLFIRI: HR = 0.422, 95%CI: 0.205 ∼ 0.870, P = 0.019, compared with FOLFOX/XELOX).

Conclusions

SNPs detection may play a predictive role in selecting first-line chemotherapy for advanced colorectal cancer patients. Radical resection of primary lesion is an independent factor for both PFS and OS.

Disclosure

All authors have declared no conflicts of interest.