Role of GST and NAT2 polymorphisms in thyroid cancer.

Genetic polymorphisms have shown to be susceptibility factors playing an important role in the development of most cancers. Nevertheless, as far as we know, only few studies have been conducted linking thyroid cancer incidence and GST polymorphisms, and no data are available on the possible association between NAT2 polymorphisms and thyroid cancer risk. The possible relationship between polymorphism at the GSTM1, GSTT1, GSTP1, and NAT2 genes and increased susceptibility to thyroid cancer has been evaluated in 176 thyroid cancer patients and 167 healthy controls, all from the urban district of Barcelona (Spain). The results indicate a clear role of the C481T change, present in several NAT2*5 alleles [odds ratio (OR)=0.58; 95% confidence interval (95% CI)=0.35-0.98]. Thus, those individuals carrying this change are less prone to develop thyroid cancer, mainly of the papillary type. In addition, there is a tendency towards the over-representation of the GSTM1 null genotype among thyroid cancer patients, particularly in those patients with papillary type tumor. The same is observed for the GSTM1 and GSTT1 null genotypes combination, and for other combinations with different NAT2 polymorphisms. The combinations involving the NAT2*6 and NAT2*7 genotypes showed the most important effect, and individuals carrying both alleles present a higher risk of thyroid cancer (OR=7.36; 95% CI=0.85-63.47), mainly for the follicular type (OR=17.94; 95% CI=1.34-238.70). The combination of NAT2*5 with NAT2*7 was also found to increase 5.26 (95% CI=1.07-25.76) times the risk of thyroid cancer. In conclusion, our results show that NAT2 polymorphisms play a significant role in thyroid cancer risk modulation.