Glutathione-S -transferase P1, T1 and M1 genetic polymorphisms in neoadjuvant-treated locally advanced gastric cancer: GSTM1-present genotype is associated with better prognosis in completely resected patients

Objective: Neoadjuvant chemotherapy in gastric cancer is now standard in the Western world; however, only 30-40% of the patients respond to induction therapy. Pretherapeutic predictors of response and prognosis would be of utmost interest to individualize treatment. Glutathione-S -transferase enzymes detoxify therapeutic drugs such as platin derivates and may influence outcome of the treated patients. Therefore, glutathione-S-transferase (GST) polymorphisms were assessed as predictive markers in cisplatinum-based neoadjuvant-treated gastric cancer. Materials and methods: DNA was isolated from 139 patients with locally advanced gastric cancer (cT3/4 anyN cM0) before chemotherapy. Multiplex polymerase chain reaction was used for GSTT1 and GSTM1 genes, and allelic discrimination assay with the TaqMan system for the GSTP1 gene. Results: One hundred ten patients could be analyzed for GSTT1 (T-:23; T+ 87), 112 for GSTM1 (M-:52; M +:60) and 132 for GSTP1 (Ile/Ile: 55; Ile/ Val: 59; Val/Val: 18). There was no significant correlation between any of the GSTT1, GSTM1, or GSTP1 genotypes and patients' characteristics or histopathological data; only the GSTM1+ genotype was associated with the non-intestinal subtype of the Lauren classification (p =0.045). GSTT1, GSTM1, and GSTP1 genotypes were not correlated with response to chemotherapy (p = 0.57, p = 0.38, p = 0.33). In R0 resected patients, we found an improved survival for patients with the GSTM1-present genotype compared to patients with the GSTM1-null genotype (p = 0.017). Moreover, the GSTM1-present genotype showed a significantly better tumor-related (p = 0.017) and disease-free survival (p = 0.029). Conclusion: None of the common GST polymorphisms predicts response in our study, but the GSTM1+ genotype was associated with a better prognosis in completely resected patients. Further investigations on chemotherapy-associated gene polymorphisms are warranted.