Common polymorphisms in TP53 and MDM2 and the relationship to TP53 mutations and clinical outcomes in women with ovarian and peritoneal carcinomas
Common polymorphisms in TP53 and MDM2 and the relationship to TP53 mutations and clinical outcomes in women with ovarian and peritoneal carcinomas
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DOI：
10.1002/gcc.20407
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发表时间：
2007-03-01
影响因子：
3.7
通讯作者：
Swisher, Elizabeth M.
中科院分区：
文献类型：
--
作者：
Galic, Vijaya;Willner, Julia;Swisher, Elizabeth M.
体细胞TP53突变和胚系TP53密码子72基因型在上皮性卵巢癌患者生存中的重要性存在争议。最近的数据表明，MDM2基因启动子的多态性可能会以一种性别特有的方式影响癌症的发病年龄。我们试图在一大系列卵巢癌和腹膜癌患者中确定体细胞TP53突变、TP53密码子72和MDM2 SNP309的胚系基因型与总体生存率和化疗反应之间的关系。在188例癌中，有103例(54.8%)存在TP53突变，其中71%为错义突变，29%为零突变。TP53突变状态和突变类型(零突变与错义突变)不影响治疗反应或总存活率。与携带一个或两个精氨酸等位基因的女性相比，携带72Pro/Pro密码子的女性总生存期(中位数为29个月)降低(中位数为49个月；P=0.04)。两个密码子72等位基因的体细胞突变或缺失同样常见。诊断年龄不受72位密码子的影响，但在携带体细胞TP53突变和MDM2 G/G基因的女性中有年轻化的趋势。(C)2006年Wiley-Liss，Inc.
The importance of somatic TP53 mutations and germline TP53 codon 72 genotype in the survival of women with epithelial ovarian cancer is controversial. Recent data suggest that a promoter polymorphism in the MDM2 gene may influence age of cancer onset in a gender-specific fashion. We sought to determine the relationship between somatic TP53 mutations, germline genotypes at TP53 codon 72 and MDM2 SNP309, and overall survival and response to chemotherapy in a large series of patients with ovarian and peritoneal carcinomas. Of the 188 cancers, 103 (54.8%) had a TP53 mutation, of which 71% were missense mutations and 29% were null mutations. TP53 mutation status and mutation type (null vs. missense) did not influence response to therapy or overall survival. Women with the codon 72 Pro/Pro had a decreased overall survival (median, 29 months) compared with women with one or two arginine alleles (median, 49 months; P = 0.04). Somatic mutation or deletion was equally common for either codon 72 allele. Age of diagnosis was not influenced by codon 72 but showed a trend for younger age in women with somatic TP53 mutations and the MDM2 G/G genotype. (c) 2006 Wiley-Liss, Inc.