Null polymorphisms in GSTT1 and GSTM1 genes and their associations with smoking and cervical cancer

Abstract

Human Papillomavirus (HPV) infection is the main risk factor for cervical cancer. However, other risk factors include smoking and genetic susceptibility. Glutathione-S-Transferases (GST) is enzymes involved in tobacco carcinogens metabolism and genes encoding these enzymes are highly polymorphic. The objective of this study was to compare the frequencies of GSTM1 and GSTT1 null polymorphisms in women with cervical cancer and in a control group, as well as the possible associations between such polymorphisms, cigarette smoking and the prognosis of cervical cancer. The series comprised 135 cervical cancer patients and 100 women without cancer. Genotypes were investigated by using polymerase chain reaction (PCR). The results were compared using the Chi-square test or Fisher's exact test, and survival analysis by Kaplan-Meier test and Log-rank. Among the cases, the frequency of GSTM1 gene null polymorphism was 22.2%, and for the GSTT1 gene it was 48.5%. Among the controls, the frequency of the GSTM1 gene null polymorphism was 45.0%, as for the GSTT1 it was 56.0%. Important association was demonstrated between smoking and cervical cancer (p=0.0062; OR=2.16). Differently from GSTM1, GSTT1 null polymorphism was not associated with cervical cancer risk in this study. GSTT1 null genotype was significantly associated to a worse prognosis. Overall survival rate for the cervical cancer group was 78.5% and, when stratified by genotypes, survival was higher in patients with positive genotypes, indicating a higher risk of death for those presenting dual nullity (p=0.031; RR=2.458).