title: 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.
authors.affiliation: Institute of Pathology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
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authors.initials: CG
authors.lastname: Stoehr
authors.affiliation: Institute of Pathology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Stoehr
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wenners
authors.affiliation: Institute of Pathology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Institute of Pathology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bertz
authors.affiliation: Institute of Pathology, Caritas Hospital Bad Mergentheim, Bad Mergentheim, Germany.
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authors.initials: V
authors.lastname: Spath
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Erlangen, Germany.|Department of Urology and Pediatric Urology, District Hospitals Altötting Burghausen, Altötting, Germany.
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authors.initials: B
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authors.affiliation: Department of Urology and Pediatric Urology, University of Saarland, Homburg/Saar, Germany.
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authors.affiliation: Department of Pathology, Institute for Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
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authors.affiliation: Institute of Pathology, Helios Hospitals Schwerin, Schwerin, Germany.
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authors.initials: R
authors.lastname: Hinze
authors.affiliation: Department of Urology, University of Regensburg, Regensburg, Germany.
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authors.affiliation: The Ludwig Institute of Cancer Research, University of Oxford, Oxford, UK.
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authors.initials: EE
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authors.affiliation: The Ludwig Institute of Cancer Research, University of Oxford, Oxford, UK.
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authors.initials: GL
authors.lastname: Bond
authors.affiliation: Institute of Legal Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Bluemke
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: K
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authors.lastname: Weigelt
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Erlangen, Germany.
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authors.lastname: Lieb
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Nolte
authors.affiliation: Department of Urology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Fornara
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Erlangen, Germany.
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authors.initials: B
authors.lastname: Wullich
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Erlangen, Germany.
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authors.lastname: Taubert
authors.affiliation: Department of Urology, Universitätsklinikum Erlangen, Erlangen, Germany.
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authors.lastname: Wach