TP53 codon 72 polymorphism in adult soft tissue sarcomas

Abstract

AbSTRACT. Soft tissue sarcomas (STS) are tumors of mesodermal origin, comprising about 1% of all adult neoplasms. Management of such tumors is an important medical challenge. TP53 codon 72 polymorphism results in either the arginine or proline form of the p53 protein; several studies have investigated whether codon 72 polymorphisms are risk and prognostic factors for cancer. We investigated p53 codon 72 polymorphism (Arg72Pro) frequencies with respect to the susceptibility and the clinical outcome of patients with STS. A series of 100 STS were genotyped for the p53 Arg72Pro polymorphism using polymerase chain reaction. Genotype frequencies were compared to a group of 85 healthy donors (controls). Possible associations between polymorphic genotypes, clinicopathological factors and survival of STS patients were also investigated. Genotypic frequencies obtained for STS patients did TP53 codon 72 polymorphism in adult soft tissue sarcomas not significantly differ from that obtained for controls. In the STS group, p53 codon 72 polymorphic variants were not significantly associated with gender, age, tumor size, clinical stage, tumor grade, histology, or nodal or distant metastasis. The five-year overall survival rate for the STS group was 48%; it was significantly affected by tumor grade, clinical stage, and nodal and distant metastasis. Soft tissue sarcoma patients with the Pro/Pro variant had a reduced survival rate (30%), when compared to the p53 Arg/Arg (45%) and the p53 Arg/Pro groups (55%). However, the differences between these groups were not significant (P = 0.44).

The functional MDM2 T309G genetic variant but not P53 Arg72Pro polymorphism is associated with risk of sarcomas: a meta-analysis

“…Of these 29 studies, 25 studies were excluded either because they were not case-control studies or they are not studies on sarcomas or reports on the role of P53 Arg72Pro on patient survival or disease progression. Among these four case-control studies, Savage et al (2007) and Toffoli et al (2009) investigated role of P53 Arg72Pro in osteosarcoma development among Caucasians, and the other two studies examined effects of this SNP on carcinogenesis of soft tissue sarcomas or Kaposi's sarcoma in mixed populations (Almeida et al 2008;Tornesello et al 2009). In addition, after searching HuGE Navigator and NCBI PubMed using the keywords ''MDM2,'' ''HDM2,'' ''sarcoma,'' ''polymorphism,'' or ''SNP,'' we found 13 studies.…”

Involvement of CYP1A1, GST, 72TP53 polymorphisms in the pathogenesis of thyroid nodules

“…Codon 72 polymorphism on the 4th exon of TP53 is involved in multiple steps of carcinogenesis and may also account for genetic differences in susceptibility to cancer (Boltze et al, 2002;Aral et al, 2007;Almeida et al, 2008). It has been demonstrated that the TP53 polymorphism varies according to ethnic and geographical distribution, like most human genetic polymorphisms.…”

Human Papillomavirus and Related Diseases - From Bench to Bedside - A Clinical Perspective

“…The most common polymorphism at codon 72 results in a nonconservative change of arginine to proline within a proline-rich region of p53, in a domain known to be important for growth suppression and apoptotic functions (Tornesello et al, 2008), may be involved in multiple steps of carcinogenesis and may also account for genetic differences in susceptibility to cancer (Reis et al, 2010b;Tornesello et al, 2008, Almeida et al, 2008. It has been demonstrated that the TP53 polymorphism distribution varies according to ethnic and geographical backgrounds, like most human genetic polymorphisms (Reis et al, 2010b).…”