Murine Double-Minute 2 Homolog Single Nucleotide Polymorphisms 285 and 309 in Cervical CarcinogenesisReport as inadecuate




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Molecular Diagnosis and Therapy

, Volume 19, Issue 4, pp 235–244

First Online: 30 July 2015

Abstract

Background and ObjectiveIn Caucasians, the MDM2 single nucleotide polymorphism SNP 285 G>C rs117039649 neutralizes the effect of 309 T>G rs2279744, which increases MDM2 expression and impairs the p53 pathway. In this study, we examined the distribution of these two SNPs in Polish women with squamous cell carcinoma SCC n = 379, adenocarcinoma n = 59 and other cervical tumor types n = 18.

MethodsThe polymerase chain reaction-restriction fragment length polymorphism technique and DNA sequencing were employed in our study.

ResultsThe P trend value calculated for the MDM2 285 G>C polymorphism was statistically significant Ptrend = 0.016 for SCC. Using logistical regression analysis adjusted for the effect of age, pregnancy, oral contraceptive use, tobacco smoking, and menopausal status, we observed that the MDM2 285 G>C SNP protected against SCC, with an adjusted odd ratio OR for the C carriers versus G-G genotype of 0.536 P = 0.019. Stratified analyses of MDM2 285 G>C revealed a protective role of the C allele against SCC in women with a positive history of oral contraceptive use age-adjusted OR 0.413, P = 0.021 and in premenopausal women age-adjusted OR 0.362, P = 0.022. We also found that the 285GG-309GG vs 285GG-309 TT genotype increased the risk of SCC adjusted OR 1.890, P = 0.005. However, the 285CC-309GG + 285GC-309GG versus 285GG-309GG genotype reduced the risk of SCC adjusted OR 0.311, P = 0.004.

ConclusionOur results demonstrate that the MDM2 285C gene variant and 285CC-309GG + 285GC-309GG genotypes protect against SCC, most likely by neutralizing the effect of the 309 T>G SNP. The 285GG-309GG genotype increases the risk of SCC possibly due to increased MDM2 expression.

Electronic supplementary materialThe online version of this article doi:10.1007-s40291-015-0153-4 contains supplementary material, which is available to authorized users.

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Author: Andrzej Roszak - Matthew Misztal - Anna Sowińska - Pawel P. Jagodziński

Source: https://link.springer.com/article/10.1007/s40291-015-0153-4



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