Murine Double-Minute 2 Homolog Single Nucleotide Polymorphisms 285 and 309 in Cervical Carcinogenesis

Abstract

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), adenocarcinoma (n = 59) and other cervical tumor types (n = 18). Methods: The polymerase chain reaction-restriction fragment 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 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). Conclusion: Our 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.