Genetic Variation in MDM2 and p14 ARF and Susceptibility to Salivary Gland Carcinoma

Background

The p14^ARF/MDM2/p53 pathway plays an important role in modulation of DNA damage and oxidative stress responses. The aim of this study was to determine whether genetic variants in MDM2 and p14^ARF are associated with risk of salivary gland carcinoma (SGC).

Methods

Four single nucleotide polymorphisms (SNPs) in MDM2 and p14^ARF (MDM2-rs2279744, MDM2-rs937283, p14^ARF-rs3731217, and p14^ARF-rs3088440) were genotyped in 156 patients with SGC and 511 cancer-free controls. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

MDM2-rs2279744 was significantly associated with a moderately increased risk of SGC (OR, 1.5, 95% CI, 1.1–2.2). There was a trend toward significantly increased SGC risk with increasing number of risk genotypes of the four polymorphisms (P _trend = 0.004). Individuals carrying 3–4 risk genotypes in MDM2 and p14^ARF were at increased SGC risk (OR, 2.0, 95% CI, 1.1–2.7) compared with individuals carrying 0–2 risk genotypes. Moreover, the combined effect of risk genotypes of MDM2 and p14^ARF was more pronounced among young subjects (≤45 years), female subjects, subjects with race/ethnicity other than non-Hispanic white, ever-smokers, and ever-drinkers.

Conclusion

Our results support the involvement of SNPs of MDM2 and p14^ARF, either alone or more likely in combination, in susceptibility to SGC. Larger studies are needed to validate our findings.