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A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA

Oncogene volume 23, pages 1954–1956 (2004)Cite this article

Abstract

We undertook a case–control study to examine the possible associations of the TP53 variants Arg>Pro at codon 72 and p53PIN3, a 16 bp insertion/duplication in intron 3, with the risk of colorectal cancer (CRC). The p53PIN3 A2 allele (16 bp duplication) was associated with an increased risk (OR 1.55, 95% CI 1.10−2.18, P=0.012), of the same order of magnitude as that observed in previous studies for other types of cancer. The Pro72 allele was weakly associated with CRC (OR=1.34, 95% CI 0.98−1.84, P=0.066). The possible functional role of p53PIN3 was investigated by examining the TP53 mRNA transcripts in 15 lymphoblastoid cell lines with different genotypes. The possibility that the insertion/deletion could lead to alternatively spliced mRNAs was excluded. However, we found reduced levels of TP53 mRNA associated with the A2 allele. In conclusion, the epidemiological study suggests a role for p53PIN3 in tumorigenesis, supported by the in vitro characterization of this variant.

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Acknowledgements

Federica Gemignani is a recipient of a fellowship from the International Association for the Study on Lung Cancer (IASLC), part of the Cancer Research Foundation of America (CRFA). Stefano Landi is a recipient of a Marie Curie fellowship (HPMFCT-2000-00483) from the European Commission. S Gutièrrez-Enriquez and N Moullan are recipients of Special Training Awards from the International Agency for Research on Cancer. This work was partially funded by grants from the Maraton of TV3 48/95, Fondo de Investigaciones Sanitarias FIS 96/0797, FIS 00/0027, FIS 01/1264 and SAF 00/81, and Association pour la Recherche sur le Cancer #7478.

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  1. Federica Gemignani, Victor Moreno and Stefano Landi: These authors contributed equally to the manuscript.

Authors and Affiliations

  1. International Agency for Research on Cancer (IARC), 150, Cours Albert Thomas, Lyon, 69372, France

    Federica Gemignani, Stefano Landi, Norman Moullan, Amélie Chabrier, Sara Gutiérrez-Enríquez, Janet Hall & Federico Canzian

  2. Dipartimento di Scienze dell'Uomo e Ambiente, University of Pisa, 56100, Italy

    Federica Gemignani & Stefano Landi

  3. Institut Catala d'Oncologia, Hospitalet, Barcelona, Spain

    Victor Moreno, Elisabeth Guino & Gabriel Capella

  4. Institut de Recerca Oncologica, Hospitalet, Barcelona, Spain

    Miguel Angel Peinado

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  1. Federica Gemignani
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Correspondence to Federico Canzian.

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Gemignani, F., Moreno, V., Landi, S. et al. A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA. Oncogene 23, 1954–1956 (2004). https://doi.org/10.1038/sj.onc.1207305

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