Polymorphism in apoptotic BAX (-248G>A) gene but not in anti-apoptotic BCL2 (-938C>A) gene and its protein and mRNA expression are associated with cervical intraepithelial neoplasia.
Apoptosis
; 20(10): 1347-57, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26272263
HPV is associated with cervical cancer and plays a crucial role in tumor formation. Apoptosis is regulated by different pathways involving genes that either promote (BCL2 gene) or inhibit (BAX gene) cell death. Our goal was to determine whether the BCL2-938C>A (rs2279115) and BAX-248G>A (rs4645878) single nucleotide polymorphisms (SNPs) are associated with squamous intraepithelial neoplasia (SIL) risk, and whether their phenotypic expression was impaired in these lesions. Two hundred and thirty-one cases showing SIL were classified as low SIL (LSIL, n = 101) or high SIL (HSIL, n = 130), and control subjects (n = 266) with no gynecologically proven SIL were recruited. No statistical difference in the genotype and allelic frequency of the BCL-2-938C>A polymorphism was observed among the groups. BCL2-938C/A and A/A homozygotes carriers had higher distribution of BCL-2-expressing cells in stroma in the SIL group. BCL2 mRNA-expression was not correlated with BCL2-938C>A SNPs in both groups. We did find a strong association of the BAX GG genotype and risk for SIL. No difference was observed between LSIL and HSIL groups. In BAX-248G/A and A/A homozygote carriers, the number of BAX-expressing cells was lower the epithelium area in SIL. However, mRNA expression was higher in SIL patients than in the control group. In conclusion, our data provide evidence that allele G carriers in the BAX-248G>A promoter SNP may influence the development of SIL. However, this genotype does not influence the SIL outcome. Additionally, we suggest a possible role of HPV infection in the inhibition of the expression of BAX protein, decreasing cell death, and favoring cervical carcinogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Displasia do Colo do Útero
/
Apoptose
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Proteínas Proto-Oncogênicas c-bcl-2
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Polimorfismo de Nucleotídeo Único
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Proteína X Associada a bcl-2
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Apoptosis
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Holanda