B02*There is a difference of vitamin D receptor gene (VDR) single-nucleotide polymorphisms (SNPs) frequencies between malignant melanoma patients and healthy volunteers and by sex?

Background: Malignant melanoma is notoriously heterogeneous neoplasm with deep difference in clinical and morphologic features and molecular profiling. Female melanoma patients generally exhibit longer survival than male patients. To improve our understanding of the melanoma molecular biology, we evaluated the role of gender on outcome. Then we compared the genomic DNA of a subgroup melanoma patients with that of healthy volunteers to analyze the role of VDR SNPs on the risk to develop malignant melanoma shared by sex. Patients and methods: Firstly we included 1,023 patients treated between 1987 and 2014. Disease free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method. A Cox regression model was used for univariate and multivariate analyses. In a second step the genomic DNA of 190 subgroup subjects was extracted from blood samples. We selected VDR SNPs rs2228570A > G (FokI), rs1544410C > T (Bsm1) and rs731236A > G (TaqI). SNPs were determined by Real-Time PCR using TaqMan assays. Results: Male/female (M/F) ratio was: 47.6%/52.4%. According to stage of disease at initial diagnosis, we showed a significant difference in DFS and in OS in favour of females in stage I (median DFS (mDFS) and median OS (mOS) not reached p = 0.001 and p = 0.01 respectively) and in stage II (mDFS= M/F: 4/12 months, p = 0.02; mOS= M/F: 7/16 months, p = 0.009). Furthermore women had a significant improvement in 12-year DFS and 12-year OS adjusted for Breslow thickness, ulceration, “absent” and “non brisk” tumor-infiltrating lymphocytes. Then the second phase of the study counted 190 subjects: 139 healthy volunteers (M/F= 61/78) and 51 melanoma patients (M/F= 30/21). We observed a major frequency of VDR rs2228570A in male patients and in female healthy volunteers and then VDR rs2228570G showed a higher expression in male healthy volunteers than in female patients. We noticed no differences between males and females in the frequency of the other SNPs examined. Conclusions: Our results showed that women present a better outcome if compared with men after adjusting for those variables that can reduce mortality risk in female melanoma patients. Furthermore males and females probably possessed a different VDR polymorphisms frequency that could become the object of further investigations. Then we are collecting blood samples from metastatic patients to evaluate differences of frequency of SNPs shared by sex. These results will be available at the forthcoming AIOM congress.