A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.

Authors:
Yuanyuan Xiao
Yuanyuan Xiao
Kunming Medical University
Epidemiology, Biostatistics
China
Jon G Jonasson, MD
Jon G Jonasson, MD
University of Iceland
Professor
Reykjavik | Iceland
Simon N Stacey Patrick Sulem Aslaug Jonasdottir Gisli Masson Julius Gudmundsson Daniel F Gudbjartsson Olafur T Magnusson Sigurjon A Gudjonsson Bardur Sigurgeirsson Kristin Thorisdottir Rafn Ragnarsson Kristrun R Benediktsdottir Bjørn A Nexø Anne Tjønneland Kim Overvad Peter Rudnai Eugene Gurzau Kvetoslava Koppova Kari Hemminki Cristina Corredera Victoria Fuentelsaz Pilar Grasa Sebastian Navarrete Fernando Fuertes Maria D García-Prats Enrique Sanambrosio Angeles Panadero Ana De Juan Almudena Garcia Fernando Rivera Dolores Planelles Virtudes Soriano Celia Requena Katja K Aben Michelle M van Rossum Ruben G H M Cremers Inge M van Oort Dick-Johan van Spronsen Jack A Schalken Wilbert H M Peters Brian T Helfand Jenny L Donovan Freddie C Hamdy Daniel Badescu Ovidiu Codreanu Mariana Jinga Irma E Csiki Vali Constantinescu Paula Badea Ioan N Mates Daniela E Dinu Adrian Constantin Dana Mates Sjofn Kristjansdottir Bjarni A Agnarsson Eirikur Jonsson Rosa B Barkardottir Gudmundur V Einarsson Fridbjorn Sigurdsson Pall H Moller Tryggvi Stefansson Trausti Valdimarsson Oskar T Johannsson Helgi Sigurdsson Thorvaldur Jonsson Laufey Tryggvadottir Terri Rice Helen M Hansen Daniel H Lachance Brian Patrick O Neill Matthew L Kosel Paul A Decker Gudmar Thorleifsson Hrefna Johannsdottir Hafdis T Helgadottir Asgeir Sigurdsson Valgerdur Steinthorsdottir Annika Lindblom Robert S Sandler Temitope O Keku Karina Banasik Torben Jørgensen Daniel R Witte Torben Hansen Oluf Pedersen Viorel Jinga David E Neal William J Catalona Margaret Wrensch John Wiencke Robert B Jenkins Eduardo Nagore Ulla Vogel Lambertus A Kiemeney Rajiv Kumar José I Mayordomo Jon H Olafsson Augustine Kong Unnur Thorsteinsdottir Thorunn Rafnar Kari Stefansson

Nat Genet 2011 Sep 25;43(11):1098-103. Epub 2011 Sep 25.

deCODE genetics, Reykjavik, Iceland.

To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).

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http://dx.doi.org/10.1038/ng.926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263694PMC
September 2011
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References

(Supplied by CrossRef)
Article in Australas. J. Dermatol.
SE de Zwaan et al.
Australas. J. Dermatol. 2010
Article in Nat. Rev. Cancer
EH Epstein et al.
Nat. Rev. Cancer 2008
Article in J. Invest. Dermatol.
NF Box et al.
J. Invest. Dermatol. 2001
Article in Nat. Genet.
DF Gudbjartsson et al.
Nat. Genet. 2008
Article in Nat. Genet.
T Rafnar et al.
Nat. Genet. 2009
Article in Nat. Genet.
SN Stacey et al.
Nat. Genet. 2008
Article in Nat. Genet.
SN Stacey et al.
Nat. Genet. 2009
Article in Nat. Genet.
A Kong et al.
Nat. Genet. 2008
Article in Nature
A Kong et al.
Nature 2009
Article in Nucleic Acids Res.
IV Kutyavin et al.
Nucleic Acids Res. 2006
Article in Nat. Rev. Cancer
C Whibley et al.
Nat. Rev. Cancer 2009

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