Association of Selected Genetic Variants in CYP1A1, CYP2D6, NAT1 and NAT2 with Endometrial Cancer Risk: A Preliminary Case–Control Study

Cancer risk may be influenced by genetic variation and altered expression of xenobiotic-metabolizing enzymes, yet their role in endometrial cancer remains incompletely understood. This study evaluated the association between four polymorphisms in xenobiotic metabolism-related genes CYP1A1 rs1799814, CYP2D6 rs3892097, NAT1 rs72554606, and NAT2 rs1799930 and the risk of endometrial cancer, and assessed CYP1A1 and CYP2D6 expression in tumor and control tissues. Genetic association analyses, including multivariate and histology-stratified models, were performed, and gene expression levels were compared between cancer and control tissues. Variants in NAT2, CYP1A1, and CYP2D6 were significantly associated with an increased risk of endometrial cancer, whereas NAT1 rs72554606 showed a protective effect, particularly in the dominant model. The strongest association was observed for NAT2 rs1799930 in additive and recessive models. Expression analysis revealed significantly higher CYP1A1 and CYP2D6 levels in tumor tissues than in control tissues. Stratified analyses showed generally consistent effects, especially for endometrioid carcinoma, although estimates for the serous subtype were limited by sample size. These findings suggest that polymorphisms and altered expression of xenobiotic-metabolizing genes may contribute to endometrial carcinogenesis. Further studies, including independent validation and analyses of gene–environment interactions, are needed.