Association of the PROGINS PgR polymorphism with susceptibility to female reproductive cancer: A meta-analysis of 30 studies

Aims: The progesterone response of the nuclear progesterone receptor plays an important role in the female reproductive system. Changes in the function of the progesterone receptor gene may increase the risk of reproductive cancer. The present study performed a meta-analysis to examine whether the progesterone receptor gene PROGINS polymorphism was a susceptibility factor for female reproductive cancer. Materials and methods: We searched the PubMed, Cochrane Library, Web of Science and EMBASE databases for literature on PROGINS polymorphisms and female reproductive cancer published before September 2020. We evaluated the risk using odds ratios [ORs] and 95% confidence intervals via fixed effects models and random-effects models, which were calculated for all five genetic models. We grouped the analyses by race, cancer, and HWE. Results: Thirty studies comprised of 25405 controls and 19253 female reproductive cancer cases were included in this meta-analysis. We observed that the Alu insertion polymorphism and the V660L polymorphism were significantly associated with female reproductive cancer in the allele and dominant genetic models. The allele genetic model and (Alu-insertion polymorphism: OR = 1.22, 95% CI = 1.02–1.45; V660L polymorphism: OR = 1.02, 95% CI = 1.00–1.13) dominant genetic model (Alu-insertion polymorphism: OR = 1.27, 95% CI = 1.03–1.58; V660L polymorphism: OR = 1.10, 95% CI = 1.011.19) demonstrated a significantly increased risk of female reproductive cancer. A subgroup analysis according to ethnicity found that the Alu insertion was associated with female reproductive cancer incidence in white (Allele model: OR = 1.21, 95% CI = 1.00–1.45; Heterozygous model: OR = 3.44, 95% CI = 1.30–9.09) and Asian (Dominant model: OR = 3.12, 95% CI = 1.25–7.79) populations, but the association disappeared for African and mixed racial groups. However, the V660L polymorphism was significantly associated with female reproductive cancer in the African (Allele model: OR = 2.52, 95% CI = 1.14–5.56; Heterozygous model: OR = 2.83, 95% CI = 1.26–6.35) and mixed racial groups (Dominant model: OR = 1.28, 95% CI = 1.01–1.62). Subgroup analysis by cancer showed that the PROGINS polymorphism increased the risk of cancer in the allele model, dominant mode and heterozygous model, but the confidence interval for this result spanned 1 and was not statistically significant. This sensitivity was verified in studies with HWE greater than 0.5. Conclusion: Our meta-analysis showed that the progesterone receptor gene Alu insertion and the V660L polymorphism contained in the PROGINS polymorphism were susceptibility factors for female reproductive cancer.