Association of MDM2 SNP309, age of onset, and gender in cutaneous melanoma.

PURPOSE: In certain cancers, MDM2 SNP309 has been associated with early tumor onset in women. In melanoma, incidence rates are higher in women than in men among individuals less than 40 years of age, but among those older than 50 years of age, melanoma is more frequent in men than in women. To investigate this difference, we examined the association among MDM2 SNP309, age at diagnosis, and gender among melanoma patients. EXPERIMENTAL DESIGN: Prospectively enrolled melanoma patients (N = 227) were evaluated for MDM2 SNP309 and the related polymorphism, p53 Arg72Pro. DNA was isolated from patient blood samples, and genotypes were analyzed by PCR-restriction fragment length polymorphism. Associations among MDM2 SNP309, p53 Arg72Pro, age at diagnosis, and clinicopathologic features of melanoma were analyzed. RESULTS: The median age at diagnosis was 13 years earlier among women with a SNP309 GG genotype (46 years) compared with women with TG+TT genotypes (59 years; P = 0.19). Analyses using age dichotomized at each decade indicated that women with a GG genotype had significantly higher risks of being diagnosed with melanoma at ages <50 years compared with women >or=50 years, but not when the comparison was made between women <60 and >or=60 years. At ages <50 years, women with a GG genotype had a 3.89 times greater chance of being diagnosed compared with women with TG+TT genotypes (P = 0.01). Similar observations were not seen among men. CONCLUSIONS: Our data suggest that MDM2 may play an important role in the development of melanoma in women. The MDM2 SNP309 genotype may help identify women at risk of developing melanoma at a young age.

MDM2 expression and regulation in prostate cancer racial disparity.

MDM2 is a key negative regulator of tumor suppressor p53. A single nucleotide polymorphism in the MDM2 promoter, SNP309, enhances transcriptional activation of MDM2 and has been associated with early onset of several types of cancer. In this study, we attempted to determine if the MDM2 SNP309 polymorphism plays a role in the aggressive phenotype seen in African American (AA) prostate cancer by examining the association between MDM2 SNP309 and MDM2 protein levels in prostate cancer (PCa) patients of different racial backgrounds. Prospectively enrolled PCa patients (AA=51, CA=50) were evaluated for MDM2 SNP309 and MDM2 protein expression. MDM2 overexpression, defined as >10% of tumor cells in three tissue cores, was assessed using immunohistochemistry on tissue microarray. MDM2 protein expression was significantly greater in CA than AA patients (78% versus 45% respectively, p=0.0007). Germline DNA was analyzed by PCR-RFLP then confirmed by DNA sequencing. MDM2 SNP309 genotype frequencies did not differ significantly between AA and CA PCa patients (AA: TT 68.6%, TG 25.5%, GG 5.9%; CA: TT 62.0%, TG 20.0%, GG 18.0%; p=0.16), suggesting that the MDM2 SNP309 allele does not play a significant role in the observed overexpression.