CEINGE Biotecnologie Avanzate, Napoli, Italy.
J Hum Genet. 2010 Aug;55(8):518-24. doi: 10.1038/jhg.2010.62. Epub 2010 Jun 10.
A functional single nucleotide polymorphism (SNP) 309 T/G within mouse double minute 2 (MDM2) gene has been linked to onset and outcome of disease in tumors. Two published studies have shown discordant results regarding the effect of this SNP on age at diagnosis of cutaneous melanoma (CM) in Caucasian female populations. Here, we examined the age at diagnosis and clinical associations of CM with SNP309 and the related polymorphism, p53 Arg72Pro, in an Italian population (249 CM patients and 291 cancer-free controls) composed of women and men. MDM2 intronic region of 294 bp was directly sequenced, whereas Arg72Pro SNP was analyzed by polymerase chain reaction-restriction fragment length polymorphism. No associations were found among the SNP309, Arg72Pro, risk of CM, age at diagnosis and presence of metastasis in total subjects and when stratified according to the gender. The SNP309 was significantly associated with tumor Breslow thickness. The P-value in the minor allele recessive mode was 0.02, and the odds ratio (OR) adjusted for gender and age was 3.11 (95% confidential interval (CI)=1.21-8.00). The SNP309 is not associated with the risk and age of onset of CM, and the presence of metastasis in an Italian population but the SNP309 GG may be a risk genotype for increasing in tumor Breslow thickness.
一个功能性的单核苷酸多态性（SNP）309T/G 位于小鼠双微体 2（MDM2）基因内，与肿瘤疾病的发病和结局有关。两项已发表的研究表明，该 SNP 对高加索女性皮肤黑色素瘤（CM）发病年龄的影响存在不一致的结果。在这里，我们在一个由女性和男性组成的意大利人群（249 例 CM 患者和 291 例无癌对照）中，检查了 SNP309 以及相关的多态性 p53Arg72Pro 与 CM 的发病年龄和临床关联。直接对 MDM2 内含子区域的 294bp 进行测序，而 Arg72Pro SNP 通过聚合酶链反应-限制性片段长度多态性分析进行分析。在总人群和按性别分层时，SNP309、Arg72Pro、CM 风险、发病年龄和转移存在之间均未发现关联。SNP309 与肿瘤 Breslow 厚度显著相关。在纯合隐性模式下的 P 值为 0.02，且性别和年龄调整后的比值比（OR）为 3.11（95%置信区间（CI）=1.21-8.00）。在意大利人群中，SNP309 与 CM 的发病风险和发病年龄以及转移的存在无关，但 SNP309 GG 可能是增加肿瘤 Breslow 厚度的风险基因型。
