Copson Ellen R, White Helen E, Blaydes Jeremy P, Robinson David O, Johnson Peter W, Eccles Diana M
Cancer Research UK Oncology Unit, Cancer Sciences Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton, SO16 6YD, UK.
BMC Cancer. 2006 Mar 24;6:80. doi: 10.1186/1471-2407-6-80.
The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1.
Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technologytrade mark was used to determine the genotype at the MDM2 SNP309 locus.
The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6%) and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G). Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T) individuals (72.7% vs. 75.6%, p = 1.00). Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80).
We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.
MDM2基因编码p53肿瘤抑制蛋白的负调控因子。据报道，MDM2启动子中的一个单核苷酸多态性（SNP）（核苷酸309处的T到G交换）会导致遗传性p53突变个体的肿瘤形成加速。我们研究了MDM2 SNP309对一组BRCA1种系突变患者临床结局的影响。
获取了102名健康对照者和116名已确诊BRCA1致病突变患者的基因组DNA，并使用焦磷酸测序技术商标来确定MDM2 SNP309位点的基因型。
该多态性在52.9%的对照者中存在（37.3%为G/T，15.6%为G/G），在58.6%的BRCA1突变携带者中存在（47.4%为G/T，11.2%为G/G）。SNP309携带者中女性BRCA1携带者的恶性肿瘤发生率并不显著高于野生型（T/T）个体（72.7%对75.6%，p = 1.00）。SNP309 G/G基因型携带者首次诊断为乳腺癌的平均年龄为41.2岁，SNP309 G/T基因型携带者为38.6岁，野生型个体为39.0岁（p = 0.80）。
我们没有发现证据表明MDM2 SNP309会加速已知BRCA1种系致病突变携带者的肿瘤发展。
