Influence of GSTT1 and GSTM1 null genotypes on differentiated thyroid cancer risk and baseline and radioiodine induced cytogenetic damage in peripheral blood lymphocytes of patients

Abstract

As it is known that genetic polymorphisms of glutathione S-transferases (GST) have been associated with a variety of human diseases including cancer, we have analyzed the impact of GSTT1 and GSTM1 null genotypes on the risk of development of differentiated thyroid cancer (DTC) and cytogenetic changes in peripheral blood lymphocytes of DTC patients before and after radioiodine therapy. The polymorphism of GSTT1 and GSTM1 genes were genotyped using multiplex polymerase chain reaction (PCR) and cytokinesis - block micronucleus (MN) assay to assess cytogenetic changes. GSTT1 and GSTM1 null were predominantly found in patients, but statistical significance was observed only for GSTT1 null. The null genotypes increased risk of development of DTC; GSTT1 null a 4.5 times (p < 0.05), GSTM1 null about 3 times but on the border of statistical significance (p = 0.057), while combination of dual null genotypes almost 7 times (p < 0.05) increased risk. No significant effects of the null genotypes as well as their interactions with potential modifiers of MN (diagnose, age, gender and smoking habits) were observed on both baseline and radioiodine-induced values of MN and cytokinesis block proliferation index (CBPI) in DTC patients. Results suggest that both GSTT1 and GSTM1 null genotypes increased risk for DTC but to a greater extent GSTT1 null. Null genotypes of GSTT1 and GSTM1 did not have potential to influence baseline and radioiodine-induced values of MN and CBPI, so that absence of T1 and M1 isoenzymes did not cause increased mutagen sensitivity of PBLs of DTC patients.