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- Title
A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- Authors
Stacey, Simon N; Sulem, Patrick; Jonasdottir, Aslaug; Masson, Gisli; Gudmundsson, Julius; Gudbjartsson, Daniel F; Magnusson, Olafur T; Gudjonsson, Sigurjon A; Sigurgeirsson, Bardur; Thorisdottir, Kristin; Ragnarsson, Rafn; Benediktsdottir, Kristrun R; Nexø, Bjørn A; Tjønneland, Anne; Overvad, Kim; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Hemminki, Kari; Corredera, Cristina; Fuentelsaz, Victoria; Grasa, Pilar; Navarrete, Sebastian; Fuertes, Fernando; García-Prats, Maria D; Sanambrosio, Enrique; Panadero, Angeles; De Juan, Ana; Garcia, Almudena; Rivera, Fernando; Planelles, Dolores; Soriano, Virtudes; Requena, Celia; Aben, Katja K; van Rossum, Michelle M; Cremers, Ruben G H M; van Oort, Inge M; van Spronsen, Dick-Johan; Schalken, Jack A; Peters, Wilbert H M; Helfand, Brian T; Donovan, Jenny L; Hamdy, Freddie C; Badescu, Daniel; Codreanu, Ovidiu; Jinga, Mariana; Csiki, Irma E; Constantinescu, Vali; Badea, Paula; Mates, Ioan N; Dinu, Daniela E; Constantin, Adrian; Mates, Dana; Kristjansdottir, Sjofn; Agnarsson, Bjarni A; Jonsson, Eirikur; Barkardottir, Rosa B; Einarsson, Gudmundur V; Sigurdsson, Fridbjorn; Moller, Pall H; Stefansson, Tryggvi; Valdimarsson, Trausti; Johannsson, Oskar T; Sigurdsson, Helgi; Jonsson, Thorvaldur; Jonasson, Jon G; Tryggvadottir, Laufey; Rice, Terri; Hansen, Helen M; Xiao, Yuanyuan; Lachance, Daniel H; O Neill, Brian Patrick; Kosel, Matthew L; Decker, Paul A; Thorleifsson, Gudmar; Johannsdottir, Hrefna; Helgadottir, Hafdis T; Sigurdsson, Asgeir; Steinthorsdottir, Valgerdur; Lindblom, Annika; Sandler, Robert S; Keku, Temitope O; Banasik, Karina; Jørgensen, Torben; Witte, Daniel R; Hansen, Torben; Pedersen, Oluf; Jinga, Viorel; Neal, David E; Catalona, William J; Wrensch, Margaret; Wiencke, John; Jenkins, Robert B; Nagore, Eduardo; Vogel, Ulla; Kiemeney, Lambertus A; Kumar, Rajiv; Mayordomo, José I; Olafsson, Jon H; Kong, Augustine; Thorsteinsdottir, Unnur; Rafnar, Thorunn; Stefansson, Kari; Swedish Low-risk Colorectal Cancer Study Group
- 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).
- Publication
Nature genetics, 2011, Vol 43, Issue 11, p1098
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.926