Glutathione S-Transferase Mu1 polymorphisms and environmental factors in cervical cancer susceptibility: a systematic review and meta-analysis.

Cervical cancer is a multifactorial disease like any other human cancer. Among these factors, genetic polymorphisms of Glutathione S-Transferase Mu1 (GSTM1) have been incriminated, but the studies results remain controversial. The objective of this meta-analysis was to study the influence of GSTM1 polymorphisms on the occurrence of cervical cancer and to explore interactions between genes and human papillomavirus (HPV) infection and exposure to tobacco smoke. A meta-analysis was conducted on studies published up to June 12, 2025, from six databases: ScienceDirect, Embase, Scopus, PubMed, Google Scholar, Web of Science. Eligible studies included all case-control investigations that assessed the association between GSTM1 polymorphisms and the risk of cervical cancer. Odds ratios and confidence intervals from the studies were used to estimate the combined effect size. Statistical analyses were conducted using both the DerSimonian and Laird random-effects model and Mantel and Haenszel fixed-effect model with a 95% confidence interval. Subgroup analyses were performed to identify potential sources of variability. A significant association was observed between the GSTM1-null and an increased risk of Cervical Cancer (ORCC=1.47, Pz=0.011) and Squamous Intraepithelial Lesions (ORSIL=1.42, Pz=0.035) compared with the GSTM1-present. The included studies showed high heterogeneity. Overall, carriers of the GSTM1-null had a higher likelihood of developing Cervical Cancer compared to carriers of the GSTM1-present. In subgroup analyses, an increased risk associated with the GSTM1-null was found among Asian populations (ORCC=1.54, Pz=0.002) and according to sample type, in blood DNA extracts (ORCC=1.27, Pz=0.052). Furthermore, the GSTM1-null was associated with increased risk in HPV+ women (ORCC=4.88, Pz=0.005) and in women exposed to tobacco smoke (ORCC=1.35, Pz=0.033). According to histological type, GSTM1-null was also associated with the development of Squamous Cell Carcinoma (ORSCC=1.52, Pz=0.020). in conclusion, GSTM1-nullwere associated with an increased risk of cervical cancer in women, especially in HPV+ women and those exposed to tobacco smoke.