The glutathione transferase omega 1-1 GSTO1∗A140D polymorphism is associated with unfavourable prognosis in patients with thymoma and myasthenia gravis.

PURPOSE: Thymomas are rare organotypic tumors frequently associated with immune-related paraneoplastic syndromes. The genetic alterations of thymomas are largely unknown and rely on general transcription factor I (GTF2I) and Harvey rat sarcoma (HRAS) mutations. Glutathione transferase omega-1-1 (GSTO1-1) is an atypical member of the glutathione transferase superfamily involved in regulating pro-survival and anti-apoptotic pathways. The association between GSTO1-1 polymorphisms and the increased risk of different types of cancer has been investigated, but no study has focused on thymomas to date. Therefore, we have investigated whether two major GSTO1-1 genetic variants, namely GSTO1∗A140D and GSTO1∗E155del polymorphisms, might represent a risk for thymoma development.

PATIENTS AND METHODS: Genotyping was performed in 47 patients diagnosed with thymoma and myasthenia gravis by using a PCR-RFLP assay.

RESULTS: The results of our study show no significant correlation between the two polymorphisms and thymoma histotype, stage, disease progression, and myasthenia gravis symptoms. A worse progression-free survival (PFS; 66.8 vs 236.6 months) was found, however, in patients bearing the homozygous GSTO1∗A140D polymorphism, suggesting a potential role for GSTO1-1 in thymoma. Indeed, enzymes with a regulatory function, such as GSTO1-1, could produce very different effects depending on both their activity and the relevance of their substrates in the risk/progression of a specific neoplasm.

CONCLUSIONS: GSTO1∗A140D polymorphism deserves to be further explored as a possible risk factor associated with a worse PFS in thymoma. Specific targets of GSTO1-1 in thymomas need to be determined.