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

• Published in: Genetics and molecular research no. 1
• Main Authors: Tacca, ALM, Lopes, AK, Vilanova-Costa, CAST, Silva, AMTC, Costa, SHN, Nogueira, NA, Ramos, JEP, Ribeiro, AA, Saddi, VA
• Format: Journal Article
• Language: English
• Published: Ribeirao Preto Fundacao de Pesquisas Cientificas de Ribeirao Preto 2019
• Subjects: Carcinogens; Cervical cancer; Cervix; Cigarette smoking; Enzymes; Gene polymorphism; Genes; Glutathione; GSTM1 gene; GSTM1 protein; GSTT1 gene; GSTT1 protein; Human papillomavirus; Medical prognosis; Polymorphism; Prognosis; Risk factors; Smoking; Survival; Survival analysis; Tobacco
• ISSN: 1676-5680
• DOI: 10.4238/gmr18067

Human papillomavirus infection is the main risk factor for cervical cancer. Other risk factors include smoking and genetic susceptibility. Glutathione-S-transferases are enzymes involved in tobacco carcinogen metabolism, and genes encoding these enzymes are highly polymorphic. We compared the frequencies of GSTM1 and GSTT1 null polymorphisms in women with cervical cancer and in a control group, as well as to determine 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 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%, while for GSTT1 it was 56.0%. A significant association was found between smoking and cervical cancer (P = 0.0062; OR = 2.16). Differently from GSTM1, the GSTT1 null polymorphism was not associated with cervical cancer risk in this study. The GSTT1 null genotype was significantly associated with worse prognosis. The overall survival rate for the cervical cancer group was 78.5%, and when stratified by genotypes, survival was higher in patients presenting at least one of the alleles, GSTT1 or GSTM1, indicating a higher risk of death for those presenting dual nullity (P = 0.031; RR = 2.458).