A germline variant in the TP53 polyadenylation signal confers cancer susceptibility

作者：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; Nexo Bjorn A; Tjonneland Anne; Overvad Kim; Rudnai Peter; Gurzau Eugene; Koppova Kvetoslava; Hemminki Kari; Corredera Cristina; Fuentelsaz Victoria; Grasa Pilar; Navarrete Sebastian; Fuertes Fernando; Garcia Prats Maria D

来源：Nature Genetics, 2011, 43(11): 1098-U85.

DOI：10.1038/ng.926

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).

• 出版日期2011-11
• 单位西北大学