1. A germline variant in the TP53 polyadenylation signal confers cancer susceptibility
- Author
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Stacey, S.N., Sulem, P., Jonasdottir, A., Masson, G., Gudmundsson, J., Gudbjartsson, D.F., Magnusson, O.T., Gudjonsson, S.A., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Nexo, B.A., Tjonneland, A., Overvad, K., Rudnai, P., Gurzau, E, Koppova, K., Hemminki, K., Corredera, C., Fuentelsaz, V., Grasa, P., Navarrete, S., Fuertes, F., Garcia-Prats, M.D., Sanambrosio, E., Panadero, A., Juan, A. de, Garcia, A., Rivera, F., Planelles, D., Soriano, V., Requena, C., Aben, K.K.H., Rossum, M.M. van, Cremers, R.G.H.M., Oort, I.M. van, Spronsen, D.J. van, Schalken, J.A., Peters, W.H.M., Helfand, B.T., Donovan, J.L., Hamdy, F.C., Badescu, D., Codreanu, O., Jinga, M., Csiki, I.E., Constantinescu, V., Badea, P., Mates, I.N., Dinu, D.E., Constantin, A., Mates, D., Kristjansdottir, S., Agnarsson, B.A., Jonsson, E., Barkardottir, R.B., Einarsson, G.V., Sigurdsson, F., Moller, P.H., Stefansson, T., Valdimarsson, T., Johannsson, O.T., Sigurdsson, H., Jonsson, T., Jonasson, J.G., Tryggvadottir, L., Rice, T., Hansen, H.M., Xiao, Y., Lachance, D.H., Kosel, M.L., Decker, P.A., Thorleifsson, G., Johannsdottir, H., Helgadottir, H.T., Sigurdsson, A., Steinthorsdottir, V., Lindblom, A., Sandler, R.S., Keku, T.O., Banasik, K., Jorgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Jinga, V., Neal, D.E., Catalona, W.J., Wrensch, M., Wiencke, J., Jenkins, R.B., Nagore, E., Vogel, U., Kiemeney, L.A.L.M., Kumar, R., Mayordomo, J.I., Olafsson, J.H., et al., Stacey, S.N., Sulem, P., Jonasdottir, A., Masson, G., Gudmundsson, J., Gudbjartsson, D.F., Magnusson, O.T., Gudjonsson, S.A., Sigurgeirsson, B., Thorisdottir, K., Ragnarsson, R., Benediktsdottir, K.R., Nexo, B.A., Tjonneland, A., Overvad, K., Rudnai, P., Gurzau, E, Koppova, K., Hemminki, K., Corredera, C., Fuentelsaz, V., Grasa, P., Navarrete, S., Fuertes, F., Garcia-Prats, M.D., Sanambrosio, E., Panadero, A., Juan, A. de, Garcia, A., Rivera, F., Planelles, D., Soriano, V., Requena, C., Aben, K.K.H., Rossum, M.M. van, Cremers, R.G.H.M., Oort, I.M. van, Spronsen, D.J. van, Schalken, J.A., Peters, W.H.M., Helfand, B.T., Donovan, J.L., Hamdy, F.C., Badescu, D., Codreanu, O., Jinga, M., Csiki, I.E., Constantinescu, V., Badea, P., Mates, I.N., Dinu, D.E., Constantin, A., Mates, D., Kristjansdottir, S., Agnarsson, B.A., Jonsson, E., Barkardottir, R.B., Einarsson, G.V., Sigurdsson, F., Moller, P.H., Stefansson, T., Valdimarsson, T., Johannsson, O.T., Sigurdsson, H., Jonsson, T., Jonasson, J.G., Tryggvadottir, L., Rice, T., Hansen, H.M., Xiao, Y., Lachance, D.H., Kosel, M.L., Decker, P.A., Thorleifsson, G., Johannsdottir, H., Helgadottir, H.T., Sigurdsson, A., Steinthorsdottir, V., Lindblom, A., Sandler, R.S., Keku, T.O., Banasik, K., Jorgensen, T., Witte, D.R., Hansen, T., Pedersen, O., Jinga, V., Neal, D.E., Catalona, W.J., Wrensch, M., Wiencke, J., Jenkins, R.B., Nagore, E., Vogel, U., Kiemeney, L.A.L.M., Kumar, R., Mayordomo, J.I., Olafsson, J.H., and et al.
- Abstract
Contains fulltext : 97569.pdf (publisher's version ) (Closed access), 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 x 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 x 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 x 10(-6)), glioma (OR = 2.35, P = 1.0 x 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 x 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).
- Published
- 2011