Impact of glutathione S-transferase genes polymorphisms on human papillomavirus infection and precancerous lesions in West African women

Abstract

Genetic polymorphisms of certain classes of glutathione S-transferase (GST), enzyme responsible for the biotransformation of drugs and xenobiotics, have been associated with risk of several cancers such as cervical cancer. The aim of this study is to investigate the impact of glutathione S-transferase M1 and T1 deletion on high-risk human papillomavirus (HR-HPV) infections and on dysplasia. A case-control study was carried out on 1069 endocervical samples from West African women including 482 HR-HPV positive and 139 patients had cervical lesions according to visual inspection with acetic acid and Lugol (VIA/VILI) screening. Deletion of the GSTM1 and GSTT1 genes was determined using conventional PCR and genotypes of HR-HPV by real-time PCR. An association with a reduced risk for HR-HPV infection was observed in Ivorian population with GSTT1-null (OR = 0.61, 95% CI = 0.40 - 0.92, p= 0.02) and GSTM1-active/GSTT1-null genotypes (OR = 0.56, 95% CI = 0.35 - 0.90, p= 0.02). In West African, women with GSTT1-null genotype had 1.72-fold higher risk for infection with HPV66 (p= 0.044) and reduced risk (OR = 0.39) for HPV35. Whereas women with GSTM1-null/GSTT1-active genotype had 2.32-fold higher risk for HPV18 infection (p= 0.042). GSTT1-null genotype was associated to cervical lesions in West African with a reduced risk (OR = 0.63, p= 0.017).  The results of the present study demonstrate that GSTT1-null could be associated with cervical lesions and HPV35 infection with reduced risk. GSTM1-null associated with GSTT1-active could play a role in increasing the risk for HPV18 infection.   Key words: Cervical cancer, GSTM1, GSTT1, HR-HPV, West Africa.