Association Of The G/G-Snp309 Variant In The Mdm2 Gene With Earlier Tumor Onset In Female Renal Cell Carcinoma Patients

Mdm2 (Human mouse double minute 2) is an important opponent of the tumor suppressor p53. The G/G variant of SNP309 in the MDM2 promoter can increase Mdm2 mRNA/protein expression and is associated with an increased risk and earlier onset of different cancers especially in Asian populations. But the frequency and impact of the G/G variant has not been studied in Caucasian renal cell carcinoma (RCC) patients. Therefore, we analyzed an unselected German cohort of 197 consecutive RCC patients and detected the G/G variant in 18 (9.1%) patients, the G/T variant in 116 (58.9%) patients and the T/T variant in 63 (32.0%) patients. Studying the association between age at tumor onset and SNP309 genotypes, no correlation was detected in the entire RCC cohort or among the male RCC patients. However, the female G/G patients (median age 59.5 years) were diagnosed 13.5 years earlier than the T/T females (median age 73 years). Next, when separating all females into two groups at their median age (68 years), 7 patients and 1 patient with the G/G variant and 9 patients and 13 patients with the T/T variant were noted in these age groups (P = 0.024). To study the age dependency of tumor onset further, a second, age-selected cohort of 205 RCC patients was analyzed, which comprised especially young and old patients. Interestingly, the G/G type occurred more often at lower tumor stages and tumor grades compared with higher stages (P = 0.039 and P = 0.004, respectively). In females, the percentage of the G/G variant was only slightly higher in the younger age group, whereas in males, the percentage of the G/G variant was remarkably higher in the younger age group (19.4% vs. 8.0%). In summary, female Caucasian RCC patients with the MDM2 SNP 309 G/G variant showed a significantly earlier tumor onset than patients with the wildtype T/T genotype. Citation Format: Christine G. Stoehr, Robert Stoehr, Antonia Wenners, Arndt Hartmann, Simone Bertz, Verena Spath, Bernhard Walter, Kerstin Junker, Holger Moch, Raoul Hintze, Stefan Denzinger, Elisabeth E. Bond, Gareth L. Bond, Karen Bluemke, Katrin Weigelt, Verena Lieb, Elke Nolte, Paolo Fornara, Bernd Wullich, Sven Wach, Helge W. Taubert. Association of the G/G-SNP309 variant in the mdm2 gene with earlier tumor onset in female renal cell carcinoma patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3700.