Background: Breast cancer is a multifactorial disease caused by complex interactions between genetic and environmental factors. Recently, a functional polymorphism, MDM2 285G>C (rs117039649), has been discovered. This polymorphism antagonizes the effect of the 309T>G (rs2279744) polymorphism on the same gene, resulting in decreased MDM2 transcription.
Methods: The MDM2 285G>C and 309T>G polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis in women with breast cancer (n=468) and controls (n=550).
Results: The odds ratio (OR) for breast cancer patients with the MDM2 285C/C and 285G/C genotypes was 0.4768 (95% confidence interval [CI] 0.2906-0.7824; p=0.0033, pcorr=0.0066). We also found a significantly lower frequency of the MDM2 285C allele in patients with breast cancer than in controls: the OR for the C allele in patients with breast cancer was 0.4930 (95% CI=0.3059-0.7947, p=0.0031, pcorr=0.0062). The p value of the chi-square test for the trend observed for the MDM2 285G>C polymorphism was statistically significant (ptrend=0.0036). The statistical power of this study amounted to 85% for the G/C or C/C genotypes and 85% for the C allele. However, we did not observe significant differences between the distribution of MDM2 309T>G genotypes and alleles in patients with breast cancer and healthy controls.
Conclusion: In a sample of the Polish population, we observed that the MDM2 285C gene variant may be a significant protective factor against breast cancer.