Mdm2-SNP309 polymorphism in prostate cancer: no evidence for association with increased risk or histopathological tumour characteristics

Abstract

The search for inherited cancer susceptibility factors is a major focus of epidemiologic cancer studies. Analyses of single-nucleotide polymorphisms (SNP) in a variety of genes revealed a correlation between a specific allele variant and cancer predisposition. Human mouse double-minute 2 protein (Mdm2) is a cellular E3 ligase capable of ubiquitination and degradation of p53. Therefore, Mdm2 is a crucial factor of cell cycle control and cell survival. The Mdm2 promoter SNP309 was shown to increase Mdm2 expression and can, thereby, inhibit the p53 pathway. This SNP was found to be associated with increased risk and early onset of various malignancies. For prostate cancer no studies are reported to date. In a case -control study we determined the distribution of the Mdm2 SNP309 in 145 male subjects with prostate cancer and in 124 male controls without any malignancy using RFLP analysis. Cases and controls showed a similar distribution of the SNP (P ¼ 0.299). Genotype distribution showed neither an association with histopathological characteristics of the tumours nor with prognosis. Age at disease onset was also not modified by the SNP. This first study of the Mdm2 SNP309 in prostate cancer patients suggests no correlation between a certain allelic variant and an increased cancer risk.

The risks, degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism: a meta-analysis

“…All studies mentioned quality control methods for genotyping, such as randomly repeated assays or validation by directed sequencing. All studies stated that the distribution of genotypes in the control groups 12,14,[16][17][18] or case subjects 13,15 was consistent with Hardy-Weinberg equilibrium ( Table 1). Jaboin et al 15 studied 206 SPC cases, including 98.06% Caucasians and only 1.94% African-Americans; we classified this study by ethnicity as a study of Caucasians.…”

“…[12][13][14][15][16][17][18] Of these studies, five studies (872 cases and 1003 controls) were used to analyse the association of the MDM2 T309G polymorphism and PCa risk. 12,14,[16][17][18] Five studies including 1485 cases of high-grade malignancy (Gleason score o7) and 927 cases of lowgrade malignancy (Gleason score ,7) were used to determine the association between the T309G polymorphism and the malignant degree. [12][13][14][15]17 Three studies including 697 advanced cases and 1403 localized cases were analysed to study the association between the T309G polymorphism and the clinical progression of cases.…”

“…12,14,[16][17][18] Five studies including 1485 cases of high-grade malignancy (Gleason score o7) and 927 cases of lowgrade malignancy (Gleason score ,7) were used to determine the association between the T309G polymorphism and the malignant degree. [12][13][14][15]17 Three studies including 697 advanced cases and 1403 localized cases were analysed to study the association between the T309G polymorphism and the clinical progression of cases. 12,13,15 The characteristics of each study are summarized in Table 1.…”

“…12,13,15 The characteristics of each study are summarized in Table 1. Five studies 12,14,[16][17][18] were included in the PCa risk analysis, and frequencymatched controls were used for age, sex and ethnicity. All seven of the studies focused on sporadic PCa (SPC) cases.…”

“…10,11 Although two polymorphic sites of the MDM2 gene (rs2279744 and rs937282) have been studied, only the rs2279744 (T309G) site has been reported frequently as a risk factor for PCa, with inconsistent results. 12,14,[16][17][18] Moreover, some researchers have investigated the relationships between the T309G polymorphism and various clinical or pathological features of PCa, [12][13][14][15][16][17][18] among which the malignant degree and clinical progression have been studied with the same stratified standards as each other. Therefore, we performed a meta-analysis of all eligible casecontrol studies and nested case-control studies to determine a more precise estimation of the PCa risk and clinical features (malignant degree and clinical progression) associated with the MDM2 T309G polymorphism.…”