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Distinct pattern of TP53 mutations in squamous cell carcinoma of the esophagus in Iran

Oncogene volume 20, pages 7368–7374 (2001)Cite this article

A Corrigendum to this article was published on 27 February 2002

Abstract

Extremely high rates of squamous cell carcinoma of the esophagus (SCCE) are observed in Iran, reflecting unknown, genetic and/or epidemiological risk factors. Among genetic alterations in SCCE, TP53 mutations are the most frequent, vary among populations, and may provide clues on etiological mechanisms. We have analysed mutations in TP53 (exons 5–8) in 98 SCCE from Iran by temporal temperature gel electrophoresis and direct sequencing. We found 58 mutations in 49 patients (50%), with a high prevalence of C to T transitions at CpG dinucleotides (29.3%). The TP53 mutation pattern in Iran was significantly different from that observed in SCCEs from high incidence areas of China and Western Europe (P=0.007). Moreover, the prevalence of mutations at A : T base pairs (transitions and transversions) was higher in men than in women (38.7% vs 11.1%, P=0.033). COX-2 overexpression was detected in 69% of the cases evaluated (24/35), without significant association with TP53 mutation. Accumulation of nitrotyrosine, a marker of protein damage by excess levels of nitric oxide, was observed in tumor cells in six of 16 cases analysed. These results are consistent with the hypothesis that several factors are involved in TP53 mutagenesis in Iran. These factors include a baseline of chronic inflammatory stress, which may have a multiplicative impact on the sensitivity of esophageal cells to exogenous factors of risk.

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Acknowledgements

The authors thank Drs P Boffetta, N Day, N Muňoz and R Montesano for stimulating discussions and helpful suggestions, and Dr B Pignatelli for advice on the use of anti-NTYR antibodies. We also thank Dr M Hollstein for discussions and exchange of data during progression of our work. P Ferrari and M Olivier are acknowledged for assistance in statistical analysis and database management. A Sepehr was supported by a Cancer Research Fellowship from the International Agency for Research on Cancer (IARC). This work was presented in part in the Abstracts of European Association for Cancer Research, EACR XVI, Halkidiki-Hellas, Greece – June 2, 2000, Session MS34, p 66.

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  1. Alireza Sepehr

    Present address: National Cancer Institute (NCI), 6116 Executive Blvd, Suite 705, Bethesda, MD 20892-8314, USA

Authors and Affiliations

  1. Group of Molecular Carcinogenesis, International Agency for Research on Cancer (IARC), 150, cours Albert-Thomas, Lyon, 69008, France

    Alireza Sepehr, Philippe Tanière, Ghislaine Martel-Planche & Pierre Hainaut

  2. Institute of Biochemistry and Biophysics, Tehran University, Enghelab Avenue, Tehran, Iran

    Abed-Ali Zia'ee

  3. National Research Center for Genetic Engineering and Biotechnology (NRCGEB), PO Box, Tehran, 14155-6343, Iran

    Ferdous Rastgar-Jazii

  4. Department of Surgery, Tehran University of Medical Sciences, Enghelab Avenue, Tehran, Iran

    Mansour Yazdanbod

  5. Department of Pathology, Iran-Mehr Hospital, Shariati Avenue, Tehran, Iran

    Gholamreza Etemad-Moghadam & Farrokh Saidi

  6. Department of Surgery, Iran-Mehr Hospital, Shariati Avenue, Tehran, Iran

    Gholamreza Etemad-Moghadam & Farrokh Saidi

  7. Department of Epidemiology, Johns Hopkins School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, Maryland, USA

    Farin Kamangar

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Correspondence to Pierre Hainaut.

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Sepehr, A., Tanière, P., Martel-Planche, G. et al. Distinct pattern of TP53 mutations in squamous cell carcinoma of the esophagus in Iran. Oncogene 20, 7368–7374 (2001). https://doi.org/10.1038/sj.onc.1204912

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