Role of GSTT 1 Polymorphisms in Cervical Cancer Risk: Influence of Human Papillomavirus Infection and Tobacco Smoke Exposure —A Systematic Review and Meta-Analysis

Abstract

Polymorphisms in certain human genes may contribute to the development of gynecological cancers. While infection with human papillomavirus (HPV) is considered the main cause, studies suggest that deletion of the Glutathione S-Transferase Thêta1 ( GSTT 1) gene is associated with an increased risk of cervical cancer. The objective of this meta-analysis was to investigate the relationship between GSTT 1 -null genotype and cervical cancer, and to assess the influence of HPV infection and exposure to tobacco smoke. Our analyses targeted articles published up to June, 13, 2025 in the Web of Science, ScienceDirect, Embase, Scopus, PubMed and Google Scholar databases. We included only case-control studies that evaluated the association between GSTT 1 polymorphisms and cervical cancer risk. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using Meta-Essentials software, applying both fixed-effect model and random-effect models. Subgroup analyses were performed to explore potential sources of heterogeneity and the influence of environmental factors, such as HPV status and tobacco smoke exposure. Thirty-five studies were included in the meta-analyses. Overall, the GSTT 1 -null genotype was associated with a significantly increased risk of cervical cancer (OR = 1.35; 95%CI = 1.03 - 1.77, p = 0.022) and high-grade intraepithelial lesions (OR = 1.50, 95%CI = 1.15 - 1.96, p = 0.001). In subgroup analysis, significant increased risk was observed, in the pooled subgroup of HPV-positive women (OR = 1.54, 95%CI = 1.09 - 2.16, p = 0.004) and in women exposed to tobacco smoke (OR = 1.31, 95%CI = 1.01 - 1.69, p = 0.019). For high-grade lesions specifically, significant associations were found in Asian populations (OR = 2.23, 95%CI = 1.18 - 4.22, p = 0.000). An association was also observed of HPV-positive infection status. Conversely, no conclusive risk was observed among women not exposed to tobacco smoke and among DNA source (OR < 1 or CI including null value). Altogether, this meta-analysis indicates that the GSTT 1 -null genotype is associated with a significant increase in the risk of cervical cancer and high-grade.