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01.04.2013 | Original Article

Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5-fluorouracil-based postoperative adjuvant chemotherapy

verfasst von: Shizhi Wang, Lulu Chen, Qinghong Zhao, Huan Rong, Meilin Wang, Weida Gong, Jianwei Zhou, Dongmei Wu, Zhengdong Zhang

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2013

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Abstract

Purpose

Several studies have examined the prognostic value of the TP53 Arg72Pro polymorphism (rs1042522) and/or MDM2 SNP309 (rs2279744) in multiple tumors. Our aim was to determine whether these two genetic variants were correlated with clinical outcome of gastric cancer.

Methods

We genotyped the two SNPs, TP53 codon 72 polymorphism and MDM2 SNP309, in 940 gastric cancer patients with complete follow-up information and analyzed the correlation between the SNPs and gastric cancer survival.

Results

The two SNPs were not significantly associated with gastric cancer survival. However, the TP53 codon 72 polymorphism had a prominent correlation with clinical outcome of patients receiving 5-fluorouracil (5-Fu)-based postoperative chemotherapy [Arg/Arg + Arg/Pro vs. Pro/Pro, adjusted hazard ratio (HR) = 1.63, 95 % confidence interval (CI) = 1.08–2.44]. Moreover, the unfavorable effect of Arg allele on survival outcome was more predominant for subgroups of older (age >60 years), male, intestinal histology type, advanced stage (T3/T4), and none metastasis of lymph node (N0) or distant (M0) (adjusted HR = 2.34, 95 % CI = 1.24–4.44 for age >60 years; 1.72, 1.10–2.69 for male; 2.30, 1.10–4.80 for intestinal; 1.62, 1.01–2.59 for T3/T4; 3.42, 1.26–9.24 for N0; and 1.62, 1.06–2.47 for M0). Among multiple chemotherapy regimens, the association was only significant in the subgroup of 5-Fu/calcium folinate plus oxaliplatin (FOLFOX) chemotherapy regimen (adjusted HR = 4.47, 95 % CI = 1.21–16.55).

Conclusions

Our findings showed that TP53 codon 72 polymorphism was associated with survival of gastric cancer patients treated with 5-Fu-based postoperative chemotherapy. The codon 72 polymorphism may be a potential prognostic factor.

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Titel: Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5-fluorouracil-based postoperative adjuvant chemotherapy
verfasst von: Shizhi Wang
Lulu Chen
Qinghong Zhao
Huan Rong
Meilin Wang
Weida Gong
Jianwei Zhou
Dongmei Wu
Zhengdong Zhang
Publikationsdatum: 01.04.2013
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2103-3

Springer Medizin

Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5-fluorouracil-based postoperative adjuvant chemotherapy