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MDM2 polymorphism associated with the development of cervical lesions in women infected with Human papillomavirus and using of oral contraceptives

Authors :
Carolina Mm Amaral
Maria Tc Muniz
Rita de Cássia Pereira de Lima
Bárbara Simas Chagas
Jacinto da Costa Silva-Neto
Valdir de Queiroz Balbino
Antonio Carlos de Freitas
Katerina Cetkovska
Ana Pad Gurgel
Sérgio Sl Paiva Júnior
Luiz Af Silva
Marcus V. Cardoso
Source :
Infectious Agents and Cancer
Publication Year :
2014
Publisher :
Springer Science and Business Media LLC, 2014.

Abstract

Background The MDM2 gene is the major negative regulator of p53, a tumor suppressor protein. Single nucleotide polymorphism in promoter region of MDM2 gene leads to increased expression resulting in higher levels of MDM2 protein. This event increases the attenuation of the p53 pathway. Polymorphisms in this gene can interfere in the regulation of cellular proliferation. We evaluated whether MDM2 SNP309 (rs2278744) associated or not with the use of oral contraceptive can heighten susceptibility to development of cervical lesions in women HPV infected. Methods MDM2 SNP309 (rs2278744) was genotyped in a total of 287 patients using the PCR-RFLP technique. The results were analyzed by UNPHASED v.3.121 and SNPStats programs. Results The three groups (SIL, LSIL and HSIL) showed no significant differences in either genotype or allelic frequencies for MDM2 polymorphisms, except when HSIL was compared with LSIL (p = 0.037; OR = 1.81). Furthermore, in the analysis of contraceptives, a significant association was found between the use of contraceptives and the MDM2 variant in the development of high-grade cervical lesions for the TG genotype (p = 0.019; OR = 2.21) when HSIL was compared with control. When HSIL was compared with LSIL (p = 0.006; OR = 2.27). Conclusion The results of this study suggest that MDM2 SNP309 might be a good marker for assessing the progression of LSIL to HSIL. In addition, they also show that oral contraceptives alone, did not have any effect on the progression or development of cervical lesions. However, they may act synergistically with MDM2 SNP309 (rs2278744) and HPV infection in the development of cervical lesions.

Details

ISSN :
17509378
Volume :
9
Database :
OpenAIRE
Journal :
Infectious Agents and Cancer
Accession number :
edsair.doi.dedup.....0c7bbaaae4596d58f3f2282523369f09
Full Text :
https://doi.org/10.1186/1750-9378-9-24