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1. Multi-omics Characterization of Response to PD-1 Inhibitors in Advanced Melanoma

Author

Trilla-Fuertes, Lucía, primary, Gámez-Pozo, Angelo, additional, Prado-Vázquez, Guillermo, additional, López-Vacas, Rocío, additional, Soriano, Virtudes, additional, Garicano, Fernando, additional, Lecumberri, M. José, additional, Rodríguez de la Borbolla, María, additional, Majem, Margarita, additional, Pérez-Ruiz, Elisabeth, additional, González-Cao, María, additional, Oramas, Juana, additional, Magdaleno, Alejandra, additional, Fra, Joaquín, additional, Martín-Carnicero, Alfonso, additional, Corral, Mónica, additional, Puértolas, Teresa, additional, Ramos-Ruiz, Ricardo, additional, Dittmann, Antje, additional, Nanni, Paolo, additional, Fresno Vara, Juan Ángel, additional, and Espinosa, Enrique, additional

Published
2023
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2. Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II)

Author

Atkinson, Victoria, Sandhu, Shahneen, Hospers, Geke, Long, Georgina V., Aglietta, Massimo, Ferrucci, Pier F., Tulyte, Skaiste, Cappellini, Gian Carlo Antonini, Soriano, Virtudes, Ali, Sayed, Poprach, Alexandr, Cesas, Alvydas, Rodriguez-Abreu, Delvys, Lau, Mike, de Jong, Egbert, Legenne, Philippe, Stein, Dara, King, Brianna, and van Thienen, Johannes V.

Published
2020
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4. Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma

Author

Trilla-Fuertes, Lucía, primary, Gámez-Pozo, Angelo, additional, Prado-Vázquez, Guillermo, additional, López-Vacas, Rocío, additional, Zapater-Moros, Andrea, additional, López-Camacho, Elena, additional, Lumbreras-Herrera, María I., additional, Soriano, Virtudes, additional, Garicano, Fernando, additional, Lecumberri, Mª José, additional, Rodríguez de la Borbolla, María, additional, Majem, Margarita, additional, Pérez-Ruiz, Elisabeth, additional, González-Cao, María, additional, Oramas, Juana, additional, Magdaleno, Alejandra, additional, Fra, Joaquín, additional, Martín-Carnicero, Alfonso, additional, Corral, Mónica, additional, Puértolas, Teresa, additional, Ramos, Ricardo, additional, Fresno Vara, Juan Ángel, additional, and Espinosa, Enrique, additional

Published
2023
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7. Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study

Author

Martín Algarra, Salvador, Soriano, Virtudes, Fernández-Morales, Luis, Berciano-Guerrero, Miguel-Ángel, Mujika, Karmele, Manzano, José Luis, Puértolas Hernández, Teresa, Soria, Ainara, Rodríguez-Abreu, Delvys, Espinosa Arranz, Enrique, Medina Martínez, Javier, Márquez-Rodas, Ivan, Rubió-Casadevall, Jordi, Ortega, María Eugenia, Jurado García, José Miguel, Lecumberri Biurrun, María José, Palacio, Isabel, Rodríguez de la Borbolla Artacho, María, Altozano, Javier Pérez, Castellón Rubio, Victoria Eugenia, García, Almudena, Luna, Pablo, Ballesteros, Anabel, Fernández, Ovidio, López Martín, Jose Antonio, Berrocal, Alfonso, and Arance, Ana

Published
2017
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9. Abstract 5416: RNA-seq and proteomics to identify response to immunotherapy in advanced melanoma: a Spanish Melanoma Group Study

Author

Trilla-Fuertes, Lucia, primary, Prado-Vazquez, Guillermo, additional, Gámez-Pozo, Angelo, additional, Lopez-Vacas, Rocio, additional, Herrera, Maria Isabel Lumbreras, additional, Soriano, Virtudes, additional, Garicano, Fernando, additional, Lecumberri, Maria Jose, additional, Rodriguez, Maria, additional, Majem, Margarita, additional, Perez, Elisabeth, additional, Gonzalez-Cao, Maria, additional, Oramas, Juana, additional, Magdaleno, Alejandra, additional, Fra, Joaquin, additional, Martin, Alfonso, additional, Corral, Monica, additional, Puertolas, Teresa, additional, Vara, Juan Angel Fresno, additional, and Espinosa, Enrique, additional

Published
2022
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11. TERT promoter mutations in melanoma survival

Author

Nagore, Eduardo, Heidenreich, Barbara, Rachakonda, Sívaramakrishna, Garcia-Casado, Zaida, Requena, Celia, Soriano, Virtudes, Frank, Christoph, Traves, Victor, Quecedo, Esther, Sanjuan-Gimenez, Josefa, Hemminki, Kari, Landi, Maria Teresa, and Kumar, Rajiv

Published
2016
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13. High nevus counts confer a favorable prognosis in melanoma patients

Author

Ribero, Simone, Davies, John R., Requena, Celia, Carrera, Cristina, Glass, Daniel, Rull, Ramon, Vidal-Sicart, Sergi, Vilalta, Antonio, Alos, Lucia, Soriano, Virtudes, Quaglino, Pietro, Traves, Victor, Newton-Bishop, Julia A., Nagore, Eduardo, Malvehy, Josep, Puig, Susana, and Bataille, Veronique

Published
2015
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15. Adjuvant therapy versus watch-and-wait post surgery for stage III melanoma: a multicountry retrospective chart review

Author

Mohr, Peter, primary, Kiecker, Felix, additional, Soriano, Virtudes, additional, Dereure, Olivier, additional, Mujika, Karmele, additional, Saiag, Philippe, additional, Utikal, Jochen, additional, Koneru, Rama, additional, Robert, Caroline, additional, Cuadros, Florencia, additional, Chacón, Matias, additional, Villarroel, Rodrigo U, additional, Najjar, Yana G, additional, Kottschade, Lisa, additional, Couselo, Eva M, additional, Koruth, Roy, additional, Guérin, Annie, additional, Burne, Rebecca, additional, Ionescu-Ittu, Raluca, additional, Perrinjaquet, Maurice, additional, and Zager, Jonathan S, additional

Published
2019
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17. Phase I study of mitonafide in solid tumors

Author

Llombart, Manuel, Poveda, Andrés, Forner, Ernesto, Fernández-Martos, Carlos, Gaspar, Cristóbal, Muñoz, Miguel, Olmos, Teresa, Ruiz, Amparo, Soriano, Virtudes, Benavides, Ana, Martin, Miguel, Schlick, Erich, and Guillem, Vicente

Published
1992
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22. Early evolution of BRAFV600 status in the blood of melanoma patients correlates with clinical outcome and identifies patients refractory to therapy

Author

Gonzalez-Cao, Maria, primary, Mayo de las Casas, Clara, additional, Jordana Ariza, Nuria, additional, Manzano, Jose L., additional, Molina-Vila, Miguel Á., additional, Soriano, Virtudes, additional, Puertolas, Teresa, additional, Balada, Ariadna, additional, Soria, Ainara, additional, Majem, Margarita, additional, Montagut, Clara, additional, Muñoz, Eva, additional, Rodriguez-Abreu, Delvys, additional, Perez, Elisabeth, additional, Garcia, Almudena, additional, Cortes, Javier, additional, Drozdowskyj, Ana, additional, Karachaliou, Niki, additional, and Rosell, Rafael, additional

Published
2018
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23. Ipilimumab and radiation in patients with unresectable melanoma brain metastases: A multicenter, open label, phase-2, Spanish Melanoma Group (GEM) study (NCT-2013-001132-22).

Author

Lopez-Martin, Jose A., primary, Arance, Ana M., additional, De La Cruz-Merino, Luis, additional, Illescas, Ana, additional, Valduvieco, Izazkun, additional, Berrocal, Alfonso, additional, López Torrecilla, José, additional, Marquez Rodas, Ivan, additional, Curiel Garcia, Maria Teresa, additional, Soriano, Virtudes, additional, Alvarez, Ana, additional, Chust Vicente, M.L., additional, Rodriguez-Abreu, Delvys, additional, Peñas Sanchez, M.C., additional, Muñoz-Couselo, Eva, additional, Aristu, Javier, additional, Gomez Caamaño, Antonio, additional, and Martin-Algarra, Salvador, additional

Published
2018
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24. Dabrafenib plus trametinib is effective in the treatment of BRAFV600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II)

Author

Atkinson, Victoria, Sandhu, Shahneen, Hospers, Geke, Long, Georgina V., Aglietta, Massimo, Ferrucci, Pier F., Tulyte, Skaiste, Cappellini, Gian Carlo Antonini, Soriano, Virtudes, Ali, Sayed, Poprach, Alexandr, Cesas, Alvydas, Rodriguez-Abreu, Delvys, Lau, Mike, de Jong, Egbert, Legenne, Philippe, Stein, Dara, King, Brianna, and van Thienen, Johannes V.

Abstract

Supplemental Digital Content is available in the text.In clinical trials, dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAFV600-mutant unresectable or metastatic melanoma. We investigated dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAFV600-mutated unresectable stage III/IV melanoma receiving dabrafenib plus trametinib as compassionate use was conducted. Treatment patterns and duration, clinical outcomes, and tolerability were evaluated. Of 271 patients, 92.6% had stage IV melanoma, including 36.5% with brain metastases. Overall, 162 patients (59.8%) were BRAFi naive and 171 (63.1%) received first-line dabrafenib plus trametinib. Among BRAFi-naive patients, the overall response rate (ORR) was 67.3%, median OS (mOS) was 20.0 months, and median progression-free survival (mPFS) was 7.5 months. In BRAFi-naive patients with known brain metastases (n= 62), ORR was 61.3%, mOS was 15.5 months, and mPFS was 6.2 months. Eighty-four patients received BRAFi monotherapy for >30 days and switched to dabrafenib plus trametinib prior to progression. Of these 84 patients, 63 had known disease status at the time of switch, and 22 improved with the combination therapy. No new safety signals were identified, and dabrafenib plus trametinib was well tolerated. Dabrafenib plus trametinib showed substantial clinical activity in NPP patients with BRAFV600-mutated unresectable or metastatic melanoma. Analysis of treatment patterns demonstrated the effectiveness of the combination in patients with brain metastases and across lines of therapy with a well tolerated and manageable safety profile.

Published
2020
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25. TERT promoter mutation subtypes and survival in stage I and II melanoma patients.

Author

Andrés‐Lencina, Juan J., Rachakonda, Sivaramakrishna, García‐Casado, Zaida, Srinivas, Nalini, Skorokhod, Alexander, Requena, Celia, Soriano, Virtudes, Kumar, Rajiv, and Nagore, Eduardo

Abstract

Mutations within the promoter of gene encoding telomerase reverse transcriptase subunit are frequent in many cancers including melanoma. Previously, the TERT promoter mutations were shown to associate with markers of poor outcome and reduced survival in patients with primary melanoma. In this study, we investigated the impact of the subtypes of TERT mutations on disease‐free and melanoma‐specific survival in 287 patients with stage I/II nonacral melanoma. Our results showed that of the three TERT promoter mutation subtypes, in multivariate models, the −138/−139 CC > TT tandem mutation associated with worst disease‐free and melanoma‐specific survival. In particular, in combination with BRAF/NRAS mutations, the −138/−139 CC > TT TERT promoter mutation associated with statistically significant poor disease‐free and melanoma‐specific survival with hazard ratios of 6.04 (95% CI 2.03–17.94, p = 0.001) and 12.59 (95% CI 2.18–72.70, p = 0.005), respectively. In contrast to the survival data, luciferase assays showed that the highest activity was observed in experiments with a promoter construct with −124 C > T mutation followed by the −138/−139 CC > TT and −146 C > T mutations, which showed similar activity. Based on previous reports, we speculate that the tandem mutation probably leads to greater genomic instability than the common TERT promoter mutations, hence the association with worst survival. However, the results from the study are only preliminary with limited patient data, therefore, require a cautious interpretation. The observations in this study, if confirmed, could have implications for melanoma patients treated with MAP‐kinase inhibitors. What's new? Mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are associated with poor outcome and reduced survival in different cancers. Here, subtypes of these mutations were investigated for their impact on survival specifically in melanoma. Among patients with stage I/II melanoma, those with the −138/−139 CC > TT TERT alteration, which occurs primarily in skin cancers, showed the poorest disease‐free and melanoma‐specific survival. The impact on survival was significantly worsened when the −138/−139 CC > TT TERT alteration was combined with BRAF/NRAS mutations. The findings could have implications for melanoma patients treated with MAP‐kinase inhibitors, which interact with BRAF/NRAS signaling networks. [ABSTRACT FROM AUTHOR]

Published
2019
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26. Abstract 468: BRAF mutation analysis in cell free tumoral DNA (cfDNA) of melanoma patients: results from the prospective study GEM1304 (Spanish Melanoma Group)

Author

Gonzalez Cao, Maria, primary, Manzano, Jose Luis, additional, Soriano, Virtudes, additional, Puertolas, Teresa, additional, Soria, Ainara, additional, Mayo, Clara, additional, Magem, Margarita, additional, Molina, Miguel Angel, additional, Montagut, Clara, additional, Muñoz, Eva, additional, Rodriguez, Delvys, additional, Perez, Elizabeth, additional, Garcia, Almudena, additional, Cortes, Javier, additional, Jordana, Nuria, additional, Rodon, Jordi, additional, Karachaliou, Niki, additional, and Rosell, Rafael, additional

Published
2016
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27. Treatment patterns of adjuvant interferon-α2b for high-risk melanoma: a retrospective study of the Grupo Español Multidisciplinar de Melanoma – Prima study

Author

Espinosa, Enrique, primary, Soriano, Virtudes, additional, Malvehy, Josep, additional, Berrocal, Alfonso, additional, Martínez de Prado, Purificación, additional, Quindós, María, additional, Soria, Ainara, additional, Márquez-Rodas, Iván, additional, Palacio, Isabel, additional, Cerezuela, Pablo, additional, López-Vivanco, Guillermo, additional, Alonso, Lorenzo, additional, Samaniego, Elia, additional, Ballesteros, Ana, additional, Puértolas, Teresa, additional, Díaz-Beveridge, Rodrigo, additional, de la Cruz-Merino, Luis, additional, López Castro, Rafael, additional, López López, Rafael, additional, Stevinson, Kendall, additional, del Barrio, Patricia, additional, Tornamira, Maria V., additional, Guillém, Vicente, additional, and Martín-Algarra, Salvador, additional

Published
2016
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28. TERTpromoter mutations in melanoma survival

Author

Nagore, Eduardo, primary, Heidenreich, Barbara, additional, Rachakonda, Sívaramakrishna, additional, Garcia-Casado, Zaida, additional, Requena, Celia, additional, Soriano, Virtudes, additional, Frank, Christoph, additional, Traves, Victor, additional, Quecedo, Esther, additional, Sanjuan-Gimenez, Josefa, additional, Hemminki, Kari, additional, Landi, Maria Teresa, additional, and Kumar, Rajiv, additional

Published
2016
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29. Local cryosurgery and imiquimod: A successful combination for the treatment of locoregional cutaneous metastasis of melanoma: A case series

Author

Rivas‐Tolosa, Nancy, primary, Ortiz‐Brugués, Ariadna, additional, Toledo‐Pastrana, Tomás, additional, Baradad, Manel, additional, Traves, Víctor, additional, Soriano, Virtudes, additional, Sanmartín, Verónica, additional, Requena, Celia, additional, Martí, Rosa, additional, and Nagore, Eduardo, additional

Published
2015
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30. Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study.

Author

Algarra, Salvador Martín, Soriano, Virtudes, Fernández-Morales, Luis, Berciano-Guerrero, Miguel-Ángel, Mujika, Karmele, Manzano, José Luis, Hernández, Teresa Puértolas, Soria, Ainara, Rodríguez-Abreu, Delvys, Arranz, Enrique Espinosa, Martínez, Javier Medina, Márquez-Rodas, Ivan, Rubió-Casadevall, Jordi, Ortega, María Eugenia, Jurado García, José Miguel, Lecumberri Biurrun, María José, Palacio, Isabel, de la Borbolla Artacho, María Rodríguez, Altozano, Javier Pérez, and Castellón Rubio, Victoria Eugenia

Published
2017
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31. A germline variant in the TP53 polyadenylation signal confers cancer susceptibility

Author

Nexø, Bjørn A, Gudbjartsson, Daniel F, Planelles, Dolores, Magnusson, Olafur T, García-Prats, Maria D, Sulem, Patrick, Overvad, Kim, Fuertes, Fernando, Soriano, Virtudes, Rudnai, Peter, Benediktsdottir, Kristrun R, Gudmundsson, Julius, Koppova, Kvetoslava, Ragnarsson, Rafn, Stacey, Simon N, Thorisdottir, Kristin, Tjønneland, Anne, Sigurgeirsson, Bardur, Garcia, Almudena, Panadero, Angeles, Masson, Gisli, De Juan, Ana, Sanambrosio, Enrique, Fuentelsaz, Victoria, Rivera, Fernando, Hemminki, Kari, Navarrete, Sebastian, Corredera, Cristina, Gurzau, Eugene, Gudjonsson, Sigurjon A, Grasa, Pilar, and Jonasdottir, Aslaug

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).

Published
2011
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32. Effect of time to sentinel-node biopsy on the prognosis of cutaneous melanoma

Author

Tejera-Vaquerizo, Antonio, primary, Nagore, Eduardo, additional, Puig, Susana, additional, Robert, Caroline, additional, Saiag, Philippe, additional, Martín-Cuevas, Paula, additional, Gallego, Elena, additional, Herrera-Acosta, Enrique, additional, Aguilera, José, additional, Malvehy, Josep, additional, Carrera, Cristina, additional, Cavalcanti, Andrea, additional, Rull, Ramón, additional, Vilalta-Solsona, Antonio, additional, Lannoy, Emilie, additional, Boutros, Celine, additional, Benannoune, Naima, additional, Tomasic, Gorana, additional, Aegerte, Philippe, additional, Vidal-Sicart, Sergi, additional, Palou, Josep, additional, Alos, LLúcia, additional, Requena, Celia, additional, Traves, Víctor, additional, Pla, Ángel, additional, Bolumar, Isidro, additional, Soriano, Virtudes, additional, Guillén, Carlos, additional, and Herrera-Ceballos, Enrique, additional

Published
2015
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33. Ipilimumab for advanced melanoma

Author

Berrocal, Alfonso, primary, Arance, Ana, additional, Lopez Martin, Jose Antonio, additional, Soriano, Virtudes, additional, Muñoz, Eva, additional, Alonso, Lorenzo, additional, Espinosa, Enrique, additional, Lopez Criado, Pilar, additional, Valdivia, Javier, additional, and Martin Algarra, Salvador, additional

Published
2014
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34. Early evolution of BRAFV600status in the blood of melanoma patients correlates with clinical outcome and identifies patients refractory to therapy

Author

Gonzalez-Cao, Maria, Mayo de las Casas, Clara, Jordana Ariza, Nuria, Manzano, Jose L., Molina-Vila, Miguel Á., Soriano, Virtudes, Puertolas, Teresa, Balada, Ariadna, Soria, Ainara, Majem, Margarita, Montagut, Clara, Muñoz, Eva, Rodriguez-Abreu, Delvys, Perez, Elisabeth, Garcia, Almudena, Cortes, Javier, Drozdowskyj, Ana, Karachaliou, Niki, and Rosell, Rafael

Abstract

Supplemental Digital Content is available in the text.Serial analysis of BRAFmutations in circulating-free DNA (cfDNA) could be of prognostic value in melanoma patients. We collected blood samples from 63 advanced BRAFV600E/Kmelanoma patients and determined BRAFV600E/Kstatus in cfDNA using a quantitative 5′-nuclease PCR-based assay. Levels of BRAFmutation in pre-cfDNAs were associated significantly with tumour burden, progression-free survival and overall survival. Changes in BRAFstatus in cfDNA after initiation of treatment (early-cfDNA) had a significant correlation with outcome. In patients with persistent BRAFmutations (n=12), progression-free survival and overall survival were 3.5 months [95% confidence interval (CI): 1.6–4.6] and 5.3 months (95% CI: 3.4–8.1) compared with 16.6 months (95% CI: 8.2–22.3) and 21.9 months (95% CI: 10.2–NR) in patients with BRAFnegativization (n=16), and 15.1 months (95% CI: 2.3–NR) and NR (95% CI: 5.1–NR) in patients who maintained their initial negative status (n=12) (P<0.0001). The median duration of response in patients with radiological response, but persistence of BRAFV600in early-cfDNA (n=5) was 4 months. Our study indicates that serial BRAFtesting in the blood of advanced melanoma identifies patients refractory to therapy.

Published
2018
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35. A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.

Author

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, Smedh, Kenneth, 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, and Smedh, Kenneth

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).

Published
2011
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37. New common variants affecting susceptibility to basal cell carcinoma

Author

Stacey, Simon N, primary, Sulem, Patrick, additional, Masson, Gisli, additional, Gudjonsson, Sigurjon A, additional, Thorleifsson, Gudmar, additional, Jakobsdottir, Margret, additional, Sigurdsson, Asgeir, additional, Gudbjartsson, Daniel F, additional, Sigurgeirsson, Bardur, additional, Benediktsdottir, Kristrun R, additional, Thorisdottir, Kristin, additional, Ragnarsson, Rafn, additional, Scherer, Dominique, additional, Hemminki, Kari, additional, Rudnai, Peter, additional, Gurzau, Eugene, additional, Koppova, Kvetoslava, additional, Botella-Estrada, Rafael, additional, Soriano, Virtudes, additional, Juberias, Pablo, additional, Saez, Berta, additional, Gilaberte, Yolanda, additional, Fuentelsaz, Victoria, additional, Corredera, Cristina, additional, Grasa, Matilde, additional, Höiom, Veronica, additional, Lindblom, Annika, additional, Bonenkamp, Johannes J, additional, van Rossum, Michelle M, additional, Aben, Katja K H, additional, de Vries, Esther, additional, Santinami, Mario, additional, Di Mauro, Maria G, additional, Maurichi, Andrea, additional, Wendt, Judith, additional, Hochleitner, Pia, additional, Pehamberger, Hubert, additional, Gudmundsson, Julius, additional, Magnusdottir, Droplaug N, additional, Gretarsdottir, Solveig, additional, Holm, Hilma, additional, Steinthorsdottir, Valgerdur, additional, Frigge, Michael L, additional, Blondal, Thorarinn, additional, Saemundsdottir, Jona, additional, Bjarnason, Hjördis, additional, Kristjansson, Kristleifur, additional, Bjornsdottir, Gyda, additional, Okamoto, Ichiro, additional, Rivoltini, Licia, additional, Rodolfo, Monica, additional, Kiemeney, Lambertus A, additional, Hansson, Johan, additional, Nagore, Eduardo, additional, Mayordomo, José I, additional, Kumar, Rajiv, additional, Karagas, Margaret R, additional, Nelson, Heather H, additional, Gulcher, Jeffrey R, additional, Rafnar, Thorunn, additional, Thorsteinsdottir, Unnur, additional, Olafsson, Jon H, additional, Kong, Augustine, additional, and Stefansson, Kari, additional

Published
2009
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38. Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits

Author

Stacey, Simon N, primary, Gudbjartsson, Daniel F, additional, Sulem, Patrick, additional, Bergthorsson, Jon T, additional, Kumar, Rajiv, additional, Thorleifsson, Gudmar, additional, Sigurdsson, Asgeir, additional, Jakobsdottir, Margret, additional, Sigurgeirsson, Bardur, additional, Benediktsdottir, Kristrun R, additional, Thorisdottir, Kristin, additional, Ragnarsson, Rafn, additional, Scherer, Dominique, additional, Rudnai, Peter, additional, Gurzau, Eugene, additional, Koppova, Kvetoslava, additional, Höiom, Veronica, additional, Botella-Estrada, Rafael, additional, Soriano, Virtudes, additional, Juberías, Pablo, additional, Grasa, Matilde, additional, Carapeto, Francisco J, additional, Tabuenca, Pilar, additional, Gilaberte, Yolanda, additional, Gudmundsson, Julius, additional, Thorlacius, Steinunn, additional, Helgason, Agnar, additional, Thorlacius, Theodora, additional, Jonasdottir, Aslaug, additional, Blondal, Thorarinn, additional, Gudjonsson, Sigurjon A, additional, Jonsson, Gudbjörn F, additional, Saemundsdottir, Jona, additional, Kristjansson, Kristleifur, additional, Bjornsdottir, Gyda, additional, Sveinsdottir, Steinunn G, additional, Mouy, Magali, additional, Geller, Frank, additional, Nagore, Eduardo, additional, Mayordomo, José I, additional, Hansson, Johan, additional, Rafnar, Thorunn, additional, Kong, Augustine, additional, Olafsson, Jon H, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional

Published
2008
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39. Erratum: Corrigendum: ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma

Author

Gudbjartsson, Daniel F, primary, Sulem, Patrick, additional, Stacey, Simon N, additional, Goldstein, Alisa M, additional, Rafnar, Thorunn, additional, Sigurgeirsson, Bardur, additional, Benediktsdottir, Kristrun R, additional, Thorisdottir, Kristin, additional, Ragnarsson, Rafn, additional, Sveinsdottir, Steinunn G, additional, Magnusson, Veronica, additional, Lindblom, Annika, additional, Kostulas, Konstantinos, additional, Botella-Estrada, Rafael, additional, Soriano, Virtudes, additional, Juberías, Pablo, additional, Grasa, Matilde, additional, Saez, Berta, additional, Andres, Raquel, additional, Scherer, Dominique, additional, Rudnai, Peter, additional, Gurzau, Eugene, additional, Koppova, Kvetoslava, additional, Kiemeney, Lambertus A, additional, Jakobsdottir, Margret, additional, Steinberg, Stacy, additional, Helgason, Agnar, additional, Gretarsdottir, Solveig, additional, Tucker, Margaret A, additional, Mayordomo, José I, additional, Nagore, Eduardo, additional, Kumar, Rajiv, additional, Hansson, Johan, additional, Olafsson, Jon H, additional, Gulcher, Jeffrey, additional, Kong, Augustine, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional

Published
2008
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40. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma

Author

Gudbjartsson, Daniel F, primary, Sulem, Patrick, additional, Stacey, Simon N, additional, Goldstein, Alisa M, additional, Rafnar, Thorunn, additional, Sigurgeirsson, Bardur, additional, Benediktsdottir, Kristrun R, additional, Thorisdottir, Kristin, additional, Ragnarsson, Rafn, additional, Sveinsdottir, Steinunn G, additional, Magnusson, Veronica, additional, Lindblom, Annika, additional, Kostulas, Konstantinos, additional, Botella-Estrada, Rafael, additional, Soriano, Virtudes, additional, Juberías, Pablo, additional, Grasa, Matilde, additional, Saez, Berta, additional, Andres, Raquel, additional, Scherer, Dominique, additional, Rudnai, Peter, additional, Gurzau, Eugene, additional, Koppova, Kvetoslava, additional, Kiemeney, Lambertus A, additional, Jakobsdottir, Margret, additional, Steinberg, Stacy, additional, Helgason, Agnar, additional, Gretarsdottir, Solveig, additional, Tucker, Margaret A, additional, Mayordomo, José I, additional, Nagore, Eduardo, additional, Kumar, Rajiv, additional, Hansson, Johan, additional, Olafsson, Jon H, additional, Gulcher, Jeffrey, additional, Kong, Augustine, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional

Published
2008
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41. Frequency and Characteristics of Familial Melanoma in Spain: The FAM-GEM-1 Study.

Author

Márquez-Rodas, Iván, Martín González, Manuel, Nagore, Eduardo, Gómez-Fernández, Cristina, Avilés-Izquierdo, Jose Antonio, Maldonado-Seral, Cayetana, Soriano, Virtudes, Majem-Tarruella, Margarita, Palomar, Virginia, Maseda, Rocio, Martín-Carnicero, Alfonso, Puertolas, Teresa, Godoy, Elena, Cerezuela, Pablo, Ochoa de Olza, Maria, Campos, Begoña, Perez-Ruiz, Elisabeth, Soria, Ainara, Gil-Arnaiz, Irene, and Gonzalez-Cao, Maria

Subjects
FAMILY history (Medicine), MELANOMA, DERMATOLOGY, ONCOLOGY, PATIENTS, CANCER risk factors
Abstract

Introduction: Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. Patients and methods: An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. Results: In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. Conclusions: Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior. [ABSTRACT FROM AUTHOR]

Published
2015
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42. Corrigendum: ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.

Author

Gudbjartsson, Daniel F, Sulem, Patrick, Stacey, Simon N, Goldstein, Alisa M, Rafnar, Thorunn, Sigurgeirsson, Bardur, Benediktsdottir, Kristrun R, Thorisdottir, Kristin, Ragnarsson, Rafn, Sveinsdottir, Steinunn G, Magnusson, Veronica, Lindblom, Annika, Kostulas, Konstantinos, Botella-Estrada, Rafael, Soriano, Virtudes, Juberías, Pablo, Grasa, Matilde, Saez, Berta, Andres, Raquel, and Scherer, Dominique

Subjects
ANIMAL coloration
Abstract

A correction to the article "ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma," that was published in the May 18, 2008 issue is presented.

Published
2008
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43. Dabrafenib plus trametinib for compassionate use in metastatic melanoma

Author

Karmele Mujika, Pablo Luna, Victoria Eugenia Castellón Rubio, Javier Pérez Altozano, María José Lecumberri Biurrun, Jose Luis Manzano, María Eugenia Ortega, Virtudes Soriano, José Antonio López Martín, Delvys Rodriguez-Abreu, Luis Antonio Fernandez-Morales, Salvador Martin Algarra, Jordi Rubió-Casadevall, Anabel Ballesteros, Almudena Garcia, Ivan Marquez-Rodas, Teresa Puértolas Hernández, María Rodríguez de la Borbolla Artacho, Ainara Soria, Enrique Espinosa Arranz, Javier Martínez, Alfonso Berrocal, José Miguel Jurado García, Isabel Palacio, Ovidio Fernández, Miguel-Ángel Berciano-Guerrero, Ana Arance, [Martin Algarra, Salvador] Clin Univ Navarra, Med Oncol, Pamplona, Spain, [Soriano, Virtudes] Inst Valenciano Oncol, Valencia, Spain, [Fernandez-Morales, Luis] Parc Tauli Sabadell Hosp Univ, Med Oncol, Sabadell, Spain, [Berciano-Guerrero, Miguel-Angel] HURyVV, Oncol Interctr, Malaga, Spain, [Berciano-Guerrero, Miguel-Angel] Inst Invest Biomed Malaga IBIMA, Malaga, Spain, [Mujika, Karmele] Inst Oncol Kutxa, Onkol, San Sebastian, Spain, [Luis Manzano, Jose] Hosp Badalona Germans Trias & Pujol, Inst Catalan Oncol, ICO Badalona, Barcelona, Spain, [Hernandez, Teresa Puertolas] Hosp Univ Miguel Servet, Med Oncol, Zaragoza, Spain, [Soria, Ainara] Hosp Univ Ramon & Cajal, Med Oncol, Madrid, Spain, [Rodriguez-Abreu, Delvys] Complejo Hosp Univ Insular Materno Infantil Gran, Med Oncol, Las Palmas Gran Canaria, Spain, [Espinosa Arranz, Enrique] Hosp Univ La Paz, Med Oncol, Madrid, Spain, [Medina Martinez, Javier] Hosp Virgen de la Salud, Med Oncol, Toledo, Spain, [Marquez-Rodas, Ivan] Hosp Gen Univ Gregorio Maranon, Med Oncol, Madrid, Spain, [Rubio-Casadevall, Jordi] Inst Catalan Oncol Girona, Girona, Spain, [Eugenia Ortega, Maria] Hosp Arnau Vilanova, Med Oncol, Lleida, Spain, [Jurado Garcia, Jose Miguel] Hosp Univ San Cecilio, Med Oncol, Granada, Spain, [Lecumberri Biurrun, Maria Jose] Complejo Hosp Navarra, Med Oncol, Pamplona, Spain, [Palacio, Isabel] Hosp Univ Cent Asturias, Med Oncol, Oviedo, Spain, [de la Borbolla Artacho, Maria Rodriguez] Hosp Univ Nuestra Senora Valme, Med Oncol, Seville, Spain, [Perez Altozano, Javier] Hosp Gen Univ Elche, Med Oncol, Alicante, Spain, [Castellon Rubio, Victoria Eugenia] Complejo Hosp Torrecardenas Almeria, Med Oncol, Almeria, Spain, [Garcia, Almudena] Hosp Marques de Valdecilla, Med Oncol, Santander, Spain, [Luna, Pablo] Hosp Univ Son Espases, Med Oncol, Palma De Mallorca, Spain, [Ballesteros, Anabel] Hosp Univ La Princesa, Med Oncol, Madrid, Spain, [Fernandez, Ovidio] Complejo Hosp Univ Ourense, Med Oncol, Orense, Spain, [Lopez Martin, Jose Antonio] Hosp Univ 12 Octubre, Med Oncol, Madrid, Spain, [Berrocal, Alfonso] Hosp Gen Univ Valencia, Med Oncol, Valencia, Spain, [Arance, Ana] Hosp Clin Barcelona, Med Oncol, Barcelona, Spain, and Novartis

Subjects
Compassionate Use Trials, Male, Survival, humanos, Resistance, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Oximes, Medicine, 030212 general & internal medicine, Neoplasm Metastasis, Multicenter, Melanoma, metástasis neoplásica, mediana edad, Aged, 80 and over, Trametinib, anciano, trametinib, protocolos de quimioterapia antineoplásica combinada, Imidazoles, BRAF inhibitors, General Medicine, adulto, análisis de supervivencia, Middle Aged, Rash, 030220 oncology & carcinogenesis, Combination, Female, medicine.symptom, Mutations, metastatic melanoma, medicine.drug, Adult, medicine.medical_specialty, Pyridones, oximas, compassionate use, Pyrimidinones, BRAF, 03 medical and health sciences, Internal medicine, melanoma, Humans, Stage IIIC, dabrafenib, Survival analysis, Aged, Retrospective Studies, business.industry, estudios retrospectivos, pirimidinonas, Dabrafenib, ensayos clínicos de uso compasivo, medicine.disease, Survival Analysis, Regimen, Braf inhibition, Vemurafenib, Spain, Therapy, piridonas, business, V600E
Abstract

The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain., Novartis have provided funding for this observational study.

Published
2017

44. A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.

Author

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

Subjects
Humans, Polymorphism, Single Nucleotide, Tumor Suppressor Protein p53 genetics, Genetic Predisposition to Disease, Germ-Line Mutation, Neoplasms genetics, Tumor Suppressor Protein p53 metabolism
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).

Published
2011
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