Mdm2 Snp309 And Melanoma Risk Among Women

11099 Background: Melanoma incidence rates vary with respect to age and gender. While melanoma incidence is higher in women than in men prior to 50 years of age, this trend reverses after age 50. This suggests that estrogen may impact melanoma development in young women. A single nucleotide polymorphism in the MDM2 gene (SNP309), which is involved in estrogen signaling, has been shown in other cancers to correlate with age at tumor onset in premenopausal women. Analysis of MDM2 SNP309 in melanoma has not been previously reported. Methods: 286 melanoma patients (121 female, 165 male, 57.5 median age) prospectively enrolled in the NYU Interdisciplinary Melanoma Cooperative Group were studied. DNA was isolated from human blood leukocytes and analyzed for SNP309 status by PCR-RFLP. Associations between SNP309 genotypes, age at tumor onset, and clinicopathologic features of melanoma were analyzed using chi-square, Fisher’s exact, Wilcoxon, and Kruskal Wallis tests. Results: The distribution of SNP309 genotypes was significantly different between women <50 years of age (n=39, GG: 33.3%) and women ≥50 years of age (n=82, GG: 15.9%) (p=0.035). Women with a GG genotype had 2.82 times the chance of being diagnosed at <50 years of age as compared to women with TG+TT genotypes (95% CI: 1.05,7.82). Women with a TT genotype had 2.57 times the chance of being diagnosed at ≥50 years of age as compared to women with GG+TG genotypes (95% CI: 1.01,6.84). Of women with primary melanoma (n=89), the age of onset was 13 years earlier among those with a GG genotype (median 46 years) as compared to TG+TT genotypes (median 59 years) (p=.185). There was no association between SNP309 and melanoma age of onset among men, or clinicopathologic features of melanoma among men or women. Conclusions: Our data suggest that premenopausal women with a GG genotype at MDM2 SNP309 may be at increased risk for the development of melanoma. Also, among postmenopausal women, the TT genotype may be a risk factor for melanoma. No significant financial relationships to disclose.