SN Stacey, P Sulem, A Jonasdottir, G Masson, J Gudmundsson, DF Gudbjartsson, OT Magnusson, SA Gudjonsson, B Sigurgeirsson, K Thorisdottir, R Ragnarsson, KR Benediktsdottir, BA Nexø, A Tjønneland, K Overvad, P Rudnai, E Gurzau, K Koppova, K Hemminki, C Corredera, V Fuentelsaz, P Grasa, S Navarrete, F Fuertes, MD García-Prats, E Sanambrosio, A Panadero, A De Juan, A Garcia, F Rivera, D Planelles, V Soriano, C Requena, KK Aben, MM van Rossum, RGHM Cremers, IM van Oort, D-J van Spronsen, JA Schalken, WHM Peters, BT Helfand, JL Donovan, FC Hamdy, D Badescu, O Codreanu, M Jinga, IE Csiki, V Constantinescu, P Badea, IN Mates, DE Dinu, A Constantin, D Mates, S Kristjansdottir, BA Agnarsson, E Jonsson, RB Barkardottir, GV Einarsson, F Sigurdsson, PH Moller, T Stefansson, T Valdimarsson, OT Johannsson, H Sigurdsson, T Jonsson, JG Jonasson, L Tryggvadottir, T Rice, HM Hansen, Y Xiao, DH Lachance, BP O Neill, ML Kosel, PA Decker, G Thorleifsson, H Johannsdottir, HT Helgadottir, A Sigurdsson, V Steinthorsdottir, A Lindblom, Swedish Low-risk Colorectal Cancer Study Group, RS Sandler, TO Keku, K Banasik, T Jørgensen, DR Witte, T Hansen, O Pedersen, V Jinga, DE Neal, WJ Catalona, M Wrensch, J Wiencke, RB Jenkins, E Nagore, U Vogel, LA Kiemeney, R Kumar, JI Mayordomo, JH Olafsson, A Kong, U Thorsteinsdottir, T Rafnar, K Stefansson
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).