Association of TNF-α (− 308 G > A) and IFN-γ (+ 874 A > T) polymorphisms with uterine fibroid risk in Egyptian women: a case-control study

Background Uterine fibroids (UFs) are common estrogen-dependent benign tumors associated with inflammatory and fibrotic processes. Cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) play important roles in immune regulation and extracellular matrix remodeling. Genetic polymorphisms in these cytokine genes may influence individual susceptibility to UFs. Aim This study aimed to examine the association between TNF-α (− 308 G > A, rs1800629) and IFN-γ (+ 874 A > T, rs2430561) polymorphisms and the risk of uterine fibroids in Egyptian women, and to explore their relationship with selected biochemical and hormonal parameters. Methods A case-control study included 100 women with uterine fibroids and 100 healthy controls. Genotyping was performed using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Serum levels of TNF-α, IFN-γ, prolactin, estradiol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), acid phosphatase (ACP), total protein, and albumin were measured using ELISA and standard biochemical assays. Statistical analysis was performed using Chi-square tests and odds ratios. Principal component analysis (PCA) and protein interaction network analysis were included as supportive exploratory approaches. Results Women with uterine fibroids showed higher levels of TNF-α, IFN-γ, prolactin, estradiol, ALT, AST, and ACP compared with controls, while total protein and albumin levels were lower. The TNF-α − 308 A allele was associated with an increased risk of UFs (A vs. G: OR = 2.17, p = 0.0003). The IFN-γ + 874 T allele was also associated with increased susceptibility (T vs. A: OR = 2.01, p = 0.001), and the TT genotype showed the highest risk (OR = 4.81, p = 0.004). No consistent genotype-related differences were observed in most biochemical parameters, except for a slight increase in estradiol levels among IFN-γ T allele carriers. PCA indicated partial separation between cases and controls, while bioinformatic analysis supported known cytokine interactions. Conclusion TNF-α (− 308 G > A) and IFN-γ (+ 874 A > T) polymorphisms may be associated with increased risk of uterine fibroids in Egyptian women. However, these findings should be interpreted with caution due to the relatively limited sample size and the lack of adjustment for potential confounding factors. The observed biochemical changes appear to be related mainly to disease status rather than specific genotypes. Further studies with larger sample sizes and functional validation are required to confirm these findings.