FC 16-10THE ROLE OF FUNCTIONAL POLYMORPHISMS AS POSSIBLE MODULATORS OF REACTIVE OXYGEN SPECIES IN CERVICAL CANCER

22. Cervical neoplasia
A. Matos 1, C. Castelão 1, S. Castaldo 1, A. Pereira Da Silva 1, M. Bicho 2, R. Medeiros 3, M.C. Bicho 2.
1Genetics Laboratory and Environmental Health Institute, Faculty of Medicine, University of Lisbon (Portugal), 2Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina da Universidade de Lisboa/ Institute of Scientific Research Bento of Rocha Cabral (Portugal), 3Molecular Oncology Group, Portuguese Institute of Oncology Porto Centre, Porto (Portugal)

Background / Objectives

The aim of this study was to investigate the genetic susceptibility of functional polymorphisms involved in the regulation of reactive oxygen species (ROS) - NADPH oxidase (NOX) subunit (p22phox) and myeloperoxidase (MPO) in cervical carcinogenesis. 


Methods

A total of 862 women, 312 cases (46 LGSL+ 32 HGSIL+ 234 ICC) (mean age of 46.20±13.2 years old) and 550 controls (mean age of 42.44±13.38 years old). In this population were determined the polymorphisms of p22phox (CYBA C242T, rs4673) and MPO (G463A, rs2333227) by PCR-RFLP. Statistical analyses were qui-square and binary logistic regression. The results were significant for P<0.05.


Results

In our population, we confirmed that age and smoking habits were risks factors for development of cervical cancer (OR=1.04, 95%CI [1.02-1.05], P<0.0001; OR=2.47, 95% [1.36-4.47], P=0.003, respectively). The A carriers of MPO polymorphism were about 5-fold of increased risk for cervical cancer (OR=5.41, 95% [2.15-13.64], P<0.0001), being dependent of age (OR=3.38, 95% [0.85-13.48], P=0.085) and independent of smoking habits (OR=3.85, 95% [1.33-11.11], P=0.013). In p22phox polymorphism, the TT genotype was a tendency for increased risk in cervical cancer (OR=3.57, 95% [0.85-13.48], P=0.057), being age and smoking habits dependents.


Conclusion

Epithelial lesions, target for HPV, are exposed to ROS, therefore, functional polymorphisms involved in the modulation of this species may influence the susceptibility for cervical cancer. The A carriers of MPO and CC genotype of ph22phox polymorphisms, associated with lower activity of macrophages, may contribute to higher susceptibility to cervical carcinogenesis.


References