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p53 codon 72 polymorphism is associated with susceptibility to hepatocellular carcinoma in the Turkish population: a case–control study

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Abstract

The tumor suppressor p53 gene plays a crucial role in preventing carcinogenesis through its ability to induce cell cycle arrest and apoptosis following DNA damage and oncogene activation. A guanine (G)/cytosine (C) common single nucleotide polymorphism (SNP) at second position of codon 72 in exon 4 of p53 gene determines a arginine (Arg) to proline (Pro) (Arg72Pro) aminoacidic substitution within the proline-rich domain of p53 protein. Arg72 and Pro72 allele are different from a biochemical and biological point of view and many reports suggest that they can modulate individual cancer susceptibility. To determine the association of the p53 Arg72Pro polymorphism with the risk of hepatocellular carcinoma (HCC) development in a Turkish population, a hospital-based case–control study was designed consisting of 119 subjects with HCC and 119 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the p53 Arg72Pro polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our data shows that the Pro/Pro genotype of the p53 Arg72Pro polymorphism is associated with increased risk of HCC development in this Turkish population (OR = 3.20, 95% CI: 1.24–8.22, P = 0.02). Furthermore, according to stratified analysis, a significant association was observed between the homozygote Pro/Pro genotype and HCC risk in the subgroups of male gender (OR = 3.01, 95% CI: 1.14–7.97, P = 0.03) and patients with hepatitis B virus (HBV)-related HCC (OR = 4.04, 95% CI: 1.46–11.15, P = 0.007). Because our results suggest for the first time that the Pro/Pro homozygote of p53 Arg72Pro polymorphism may be a genetic susceptibility factor for HCC (especially in the male gender and HBV-infected patients) in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.

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Acknowledgments

This study was funded by Çukurova University Research Fund TF2007LTP16. The authors thank all the subjects who participated in this study.

Conflict of interest

All of the authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Faculty of Medicine, Çukurova University, 01330, Adana, Turkey

    Ahmet Taner Sümbül

  2. Department of Medical Oncology, Faculty of Medicine, Başkent University, 01170, Adana, Turkey

    Ahmet Taner Sümbül

  3. Department of Gastroenterology, Faculty of Medicine, Çukurova University, 01330, Adana, Turkey

    Hikmet Akkız, Aynur Bekar, Ersin Akgöllü & Macit Sandıkçı

  4. Adıyaman School of Health, Department of Nursing, Adıyaman University, 02040, Adıyaman, Turkey

    Süleyman Bayram

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  1. Ahmet Taner Sümbül
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  2. Hikmet Akkız
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  4. Aynur Bekar
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Correspondence to Süleyman Bayram.

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Ahmet Taner Sümbül, Hikmet Akkız and Süleyman Bayram contributed equally to this work.

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Sümbül, A.T., Akkız, H., Bayram, S. et al. p53 codon 72 polymorphism is associated with susceptibility to hepatocellular carcinoma in the Turkish population: a case–control study. Mol Biol Rep 39, 1639–1647 (2012). https://doi.org/10.1007/s11033-011-0903-2

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  • DOI: https://doi.org/10.1007/s11033-011-0903-2

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