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

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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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Acknowledgments

This study was partly supported by the National Natural Science Foundation of China (81230068, 30972444, 81001274, and 81102089), the Undergraduates Practice and Innovation Program of Higher School in Jiangsu Province, the Key Program of Natural Science Foundation of Jiangsu Province (BK2010080), National Science Foundation of Jiangsu Province (BK2011773 and BK2012842), the Key Program for Basic Research of Jiangsu Provincial Department of Education (11KJB330002 and 12KJA330002), the Qing-Lan Project of Jiangsu Provincial Department of Education, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). We thank Yanyan Zhu, Weiwei Zhuang, Hanying Lu, and Mao Liu for participating part of epidemiology investigation and experiments.

Conflict of interest

The authors declare no conflict of interests exist in relation to the publication of this study.

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Authors and Affiliations

  1. Department of Environmental Genomics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, 818 East Tianyuan Road, Nanjing, 211166, China

    Shizhi Wang, Meilin Wang, Jianwei Zhou, Dongmei Wu & Zhengdong Zhang

  2. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China

    Shizhi Wang, Lulu Chen, Huan Rong, Meilin Wang, Jianwei Zhou, Dongmei Wu & Zhengdong Zhang

  3. Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, China

    Qinghong Zhao

  4. Department of Surgery, Yixing Cancer Hospital, Yixing, China

    Weida Gong

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  1. Shizhi Wang
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  2. Lulu Chen
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Correspondence to Dongmei Wu or Zhengdong Zhang.

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Shizi Wang, Lulu Chen and Qinghong Zhao contributed equally to this work.

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Wang, S., Chen, L., Zhao, Q. et al. Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5-fluorouracil-based postoperative adjuvant chemotherapy. Cancer Chemother Pharmacol 71, 1073–1082 (2013). https://doi.org/10.1007/s00280-013-2103-3

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