Homozygous G/G variant of SNP309 in the human MDM2 gene is associated with earlier tumor onset in Caucasian female renal cell carcinoma patients

Abstract

Human mouse double minute 2 (Mdm2) plays an essential role in the regulation of the tumor suppressor p53. The G/G variant of SNP309 was shown to increase Mdm2 mRNA/protein expression and to be associated with an increased risk and earlier onset of different cancers in Asian populations. However, the frequency and impact of these G/G variants have 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). When separating all females into two groups at their median age (68 years), 7 and 1 patients with the G/G variant and 9 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 investigated, 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 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 SNP309 G/G genotype showed significantly earlier tumor onset than patients with the wild-type T/T genotype.

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“…A similar but distinct finding was reported from the use of an unselected German cohort of 197 consecutive RCC patients [ 117 ]. Among this RCC cohort, the GG, GT and TT variants were detected in turn in 18/197 (GG, 9.1%), 116/197 (GT, 58.9%) and 63/197 (TT, 32.0%) RCC patients [ 117 ].…”

“…A similar but distinct finding was reported from the use of an unselected German cohort of 197 consecutive RCC patients [ 117 ]. Among this RCC cohort, the GG, GT and TT variants were detected in turn in 18/197 (GG, 9.1%), 116/197 (GT, 58.9%) and 63/197 (TT, 32.0%) RCC patients [ 117 ]. Interestingly, this study indicated that there is no association between age at tumor onset and MDM2-SNP309 genotypes from the analysis of the entire RCC cohort or among the male RCC patients, the female GG patients (median age 59.5 years) were diagnosed 13.5 years earlier than the TT females (median age 73 years) [ 117 ].…”

“…Interestingly, this study indicated that there is no association between age at tumor onset and MDM2-SNP309 genotypes from the analysis of the entire RCC cohort or among the male RCC patients, the female GG patients (median age 59.5 years) were diagnosed 13.5 years earlier than the TT females (median age 73 years) [ 117 ]. In order to further study the age dependency of tumor onset, a second, age-selected cohort of 205 RCC patients was investigated, and the result indicated that (1) the GG type occurs more often at lower tumor stages and tumor grades compared with higher stages; and (2) while the percentage of the GG variant was only slightly higher in the female younger age group, the percentage of the GG variant was remarkably higher in the male younger age group versus the old age group (19.4% vs 8.0%) [ 117 ]. These authors concluded that female Caucasian RCC patients with the MDM2-SNP309 GG genotype have significantly earlier tumor onset than patients with the wild-type TT genotype [ 117 ].…”

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“…However, worse prognosis and low survival were displayed in patients with the MDM2 SNP309GG genotype, indicating that the polymorphism of MDM2 might be an independent poor prognostic factor for RCC [82]. In Caucasian female RCC patients, the homozygous G/G genotype of human MDM2 SNP309 is correlated with early onset [83].…”