Polymorphisms in p53, GSTP1 and XRCC1 predict relapse and survival of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy

Abstract

Purpose: The aim of this study was to assess whether genetic polymorphisms in p53, glutathione S-transferase P1 (GSTP1), GSTM1, excision repair cross complementing group 1 (ERCC1) and X-ray repair cross-complementing group 1 (XRCC1) genes are associated with clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy.

Methods: The genetic polymorphisms in p53, GSTP1, GSTM1 (null), ERCC1 and XRCC1 were determined in 102 gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy using polymerase chain reaction-ligation detection reaction method.

Results: Among the five studied polymorphisms, p53 codon 72 Pro/Pro, GSTP1 codon 105 Ile/Ile, and XRCC1 codon 399 Gln/Gln + Arg/Gln were associated with poor relapse-free survival and overall survival (P < 0.05); and the prognostic effect was retained in the Cox multivariate analysis. Combination analysis with the three polymorphisms using the Kaplan-Meier method and Cox multivariate analysis revealed that the relapse-free and overall survivals significantly increase with the number of favorable genotypes (P < 0.05). No significant association was found between the GSTM1 (null) or the ERCC1 codon 118 genotypes and the clinical outcome (P > 0.05).

Conclusion: Testing for p53 Arg72Pro, GSTP1 Ile105Val, and XRCC1 Arg399Gln polymorphisms may allow identification of gastric cancer patients who will benefit from oxaliplatin-based adjuvant chemotherapy. Selecting specific adjuvant treatments according to the individual genetic background may represent an innovative strategy that warrants prospective studies.