ORIGINAL RESEARCH ARTICLE Murine Double-Minute 2 Homolog Single Nucleotide

The Author(s) 2015. This article is published with open access at Springerlink.com Background and Objective In 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), adenocarci-noma (n = 59) and other cervical tumor types (n = 18). Methods The polymerase chain reaction-restriction frag-ment length polymorphism technique and DNA sequencing were employed in our study. Results The P trend value calculated for the MDM2 285 G[C polymorphism was statistically significant (Ptrend = 0.016) for SCC. Using logistical regression anal-ysis adjusted for the effect of age, pregnancy, oral contra-ceptive 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 (ad-justed 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). Conclusion Our results demonstrate that theMDM2 285C gene variant and 285CC/309GG? 285GC/309GG geno-types 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