A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
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 pha...
| Príomhchruthaitheoirí: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formáid: | Journal article |
| Teanga: | English |
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2011
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| _version_ | 1826295611650998272 |
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| author | Stacey, SN Sulem, P Jonasdottir, A Masson, G Gudmundsson, J Gudbjartsson, D Magnusson, O Gudjonsson, SA Sigurgeirsson, B Thorisdottir, K Ragnarsson, R Benediktsdottir, K Nexø, B Tjønneland, A Overvad, K Rudnai, P Gurzau, E Koppova, K Hemminki, K Corredera, C Fuentelsaz, V Grasa, P Navarrete, S Fuertes, F García-Prats, MD |
| author_facet | Stacey, SN Sulem, P Jonasdottir, A Masson, G Gudmundsson, J Gudbjartsson, D Magnusson, O Gudjonsson, SA Sigurgeirsson, B Thorisdottir, K Ragnarsson, R Benediktsdottir, K Nexø, B Tjønneland, A Overvad, K Rudnai, P Gurzau, E Koppova, K Hemminki, K Corredera, C Fuentelsaz, V Grasa, P Navarrete, S Fuertes, F García-Prats, MD |
| author_sort | Stacey, SN |
| collection | OXFORD |
| description | 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). |
| first_indexed | 2024-03-07T04:03:43Z |
| format | Journal article |
| id | oxford-uuid:c5716a21-fd9c-4ab8-abc2-6e1619faf711 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:03:43Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:c5716a21-fd9c-4ab8-abc2-6e1619faf7112022-03-27T06:30:58ZA germline variant in the TP53 polyadenylation signal confers cancer susceptibility.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c5716a21-fd9c-4ab8-abc2-6e1619faf711EnglishSymplectic Elements at Oxford2011Stacey, SNSulem, PJonasdottir, AMasson, GGudmundsson, JGudbjartsson, DMagnusson, OGudjonsson, SASigurgeirsson, BThorisdottir, KRagnarsson, RBenediktsdottir, KNexø, BTjønneland, AOvervad, KRudnai, PGurzau, EKoppova, KHemminki, KCorredera, CFuentelsaz, VGrasa, PNavarrete, SFuertes, FGarcía-Prats, MDTo 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). |
| spellingShingle | Stacey, SN Sulem, P Jonasdottir, A Masson, G Gudmundsson, J Gudbjartsson, D Magnusson, O Gudjonsson, SA Sigurgeirsson, B Thorisdottir, K Ragnarsson, R Benediktsdottir, K Nexø, B Tjønneland, A Overvad, K Rudnai, P Gurzau, E Koppova, K Hemminki, K Corredera, C Fuentelsaz, V Grasa, P Navarrete, S Fuertes, F García-Prats, MD A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. |
| title | A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. |
| title_full | A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. |
| title_fullStr | A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. |
| title_full_unstemmed | A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. |
| title_short | A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. |
| title_sort | germline variant in the tp53 polyadenylation signal confers cancer susceptibility |
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