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Association of Selected Genetic Variants in CYP1A1, CYP2D6, NAT1 and NAT2 with Endometrial Cancer Risk: A Preliminary
Maciej Skrzypek1, Monika Gogolewska1, Andrzej Bieńkiewicz2
1Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland.
International Journal of Molecular Sciences
|July 15, 2026
Summary
Genetic variations in xenobiotic-metabolizing enzymes like NAT2, CYP1A1, and CYP2D6 are linked to endometrial cancer risk. Higher CYP1A1 and CYP2D6 expression in tumors suggests their role in cancer development.
Area of Science:
- Genetics
- Oncology
- Pharmacogenomics
Background:
- Endometrial cancer risk is influenced by genetic factors and xenobiotic metabolism.
- The specific roles of xenobiotic-metabolizing enzymes in endometrial cancer are not fully understood.
Purpose of the Study:
- To investigate the association between polymorphisms in NAT1, NAT2, CYP1A1, and CYP2D6 genes and endometrial cancer risk.
- To compare the expression levels of CYP1A1 and CYP2D6 in endometrial tumor and control tissues.
Main Methods:
- Genotyping of four specific gene polymorphisms (CYP1A1 rs1799814, CYP2D6 rs3892097, NAT1 rs72554606, NAT2 rs1799930).
- Statistical analyses including multivariate and histology-stratified models.
- Quantitative assessment of CYP1A1 and CYP2D6 gene expression in tumor versus normal tissues.
Main Results:
- NAT2, CYP1A1, and CYP2D6 variants were associated with increased endometrial cancer risk.
- NAT1 rs72554606 demonstrated a protective effect, particularly in the dominant model.
- Elevated CYP1A1 and CYP2D6 expression was observed in tumor tissues compared to controls.
Conclusions:
- Genetic variations and altered expression of xenobiotic-metabolizing genes are implicated in endometrial carcinogenesis.
- Specific polymorphisms in NAT2, CYP1A1, and CYP2D6 may increase risk, while NAT1 may offer protection.
- Further research is warranted to validate findings and explore gene-environment interactions.
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