A germline variant in the TP53 polyadenylation signal confers cancer susceptibility View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-11

AUTHORS

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, Jon G Jonasson, Laufey Tryggvadottir, Terri Rice, Helen M Hansen, Yuanyuan Xiao, 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, Swedish Low-risk Colorectal Cancer Study Group, 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

ABSTRACT

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). More... »

PAGES

1098

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.926

DOI

http://dx.doi.org/10.1038/ng.926

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008953785

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21946351


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