Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma
Background and objective: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods: We...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2014 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/124211 |
| Acesso em linha: | https://hdl.handle.net/2445/124211 |
| Access Level: | acceso abierto |
| Palavra-chave: | Càncer de pàncrees Polimorfisme genètic Pancreas cancer Genetic polymorphisms |
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Genome-wide Association Study Of Survival In Patients With Pancreatic AdenocarcinomaWu, ChenKraft, PeterStolzenberg-Solomon, Rachael Z.Steplowski, EmilyBrotzman, MichelleXu, MoushengMudgal, PoorvaAmundadottir, LaufeyArslan, Alan A.Bueno de Mesquita, H. BasGross, Myron D.Helzlsouer, Kathy J.Jacobs, Eric J.Kooperberg, CharlesPetersen, Gloria M.Zheng, WeiAlbanes, DemetriusBoutron-Ruault, Marie-ChristineBuring, Julie E.Canzian, FedericoCao, GuangwenDuell, Eric J.Elena, Joanne W.Gaziano, J. Michael M.Giovannucci, Edward L.Hallmans, GöranHutchinson, AmyHunter, David J.Jenab, MazdaJiang, GuoliangKhaw, Kay-TeeLaCroix, AndreaLi, ZhaoshenMendelsohn, Julie B.Panico, SalvatorePatel, Alpa V.Qian, ZhirongSesso, Howard D.Shen, HongbingShu, Xiao-OuTjønneland, AnneTobias, Geoffrey S.Trichopoulos, DimitriosVirtamo, JarmoVisvanathan, KalaWactawski-Wende, JeanWang, ChengfengYu, KaiZeleniuch-Jacquotte, AnneChanock, Stephen J.Hoover, Robert N.Hartge, PatriciaFuchs, Charles S.Lin, DongxinWolpin, Brian M.Càncer de pàncreesPolimorfisme genèticPancreas cancerGenetic polymorphismsBackground and objective: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). Results: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63x10(-7)), rs981621 (p=1.65x10(-7)) and rs16861827 (p=3.75x10(-7)), respectively. 131 SNPs with p10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72x10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Conclusions: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.BMJ Publishing Group2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/124211Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1136/gutjnl-2012-303477Gut, 2014, vol. 63, num. 1https://doi.org/10.1136/gutjnl-2012-303477(c) BMJ Publishing Group Ltd; British Society of Gastroenterology, 2014info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1242112026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma |
| title |
Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma |
| spellingShingle |
Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma Wu, Chen Càncer de pàncrees Polimorfisme genètic Pancreas cancer Genetic polymorphisms |
| title_short |
Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma |
| title_full |
Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma |
| title_fullStr |
Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma |
| title_full_unstemmed |
Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma |
| title_sort |
Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma |
| dc.creator.none.fl_str_mv |
Wu, Chen Kraft, Peter Stolzenberg-Solomon, Rachael Z. Steplowski, Emily Brotzman, Michelle Xu, Mousheng Mudgal, Poorva Amundadottir, Laufey Arslan, Alan A. Bueno de Mesquita, H. Bas Gross, Myron D. Helzlsouer, Kathy J. Jacobs, Eric J. Kooperberg, Charles Petersen, Gloria M. Zheng, Wei Albanes, Demetrius Boutron-Ruault, Marie-Christine Buring, Julie E. Canzian, Federico Cao, Guangwen Duell, Eric J. Elena, Joanne W. Gaziano, J. Michael M. Giovannucci, Edward L. Hallmans, Göran Hutchinson, Amy Hunter, David J. Jenab, Mazda Jiang, Guoliang Khaw, Kay-Tee LaCroix, Andrea Li, Zhaoshen Mendelsohn, Julie B. Panico, Salvatore Patel, Alpa V. Qian, Zhirong Sesso, Howard D. Shen, Hongbing Shu, Xiao-Ou Tjønneland, Anne Tobias, Geoffrey S. Trichopoulos, Dimitrios Virtamo, Jarmo Visvanathan, Kala Wactawski-Wende, Jean Wang, Chengfeng Yu, Kai Zeleniuch-Jacquotte, Anne Chanock, Stephen J. Hoover, Robert N. Hartge, Patricia Fuchs, Charles S. Lin, Dongxin Wolpin, Brian M. |
| author |
Wu, Chen |
| author_facet |
Wu, Chen Kraft, Peter Stolzenberg-Solomon, Rachael Z. Steplowski, Emily Brotzman, Michelle Xu, Mousheng Mudgal, Poorva Amundadottir, Laufey Arslan, Alan A. Bueno de Mesquita, H. Bas Gross, Myron D. Helzlsouer, Kathy J. Jacobs, Eric J. Kooperberg, Charles Petersen, Gloria M. Zheng, Wei Albanes, Demetrius Boutron-Ruault, Marie-Christine Buring, Julie E. Canzian, Federico Cao, Guangwen Duell, Eric J. Elena, Joanne W. Gaziano, J. Michael M. Giovannucci, Edward L. Hallmans, Göran Hutchinson, Amy Hunter, David J. Jenab, Mazda Jiang, Guoliang Khaw, Kay-Tee LaCroix, Andrea Li, Zhaoshen Mendelsohn, Julie B. Panico, Salvatore Patel, Alpa V. Qian, Zhirong Sesso, Howard D. Shen, Hongbing Shu, Xiao-Ou Tjønneland, Anne Tobias, Geoffrey S. Trichopoulos, Dimitrios Virtamo, Jarmo Visvanathan, Kala Wactawski-Wende, Jean Wang, Chengfeng Yu, Kai Zeleniuch-Jacquotte, Anne Chanock, Stephen J. Hoover, Robert N. Hartge, Patricia Fuchs, Charles S. Lin, Dongxin Wolpin, Brian M. |
| author_role |
author |
| author2 |
Kraft, Peter Stolzenberg-Solomon, Rachael Z. Steplowski, Emily Brotzman, Michelle Xu, Mousheng Mudgal, Poorva Amundadottir, Laufey Arslan, Alan A. Bueno de Mesquita, H. Bas Gross, Myron D. Helzlsouer, Kathy J. Jacobs, Eric J. Kooperberg, Charles Petersen, Gloria M. Zheng, Wei Albanes, Demetrius Boutron-Ruault, Marie-Christine Buring, Julie E. Canzian, Federico Cao, Guangwen Duell, Eric J. Elena, Joanne W. Gaziano, J. Michael M. Giovannucci, Edward L. Hallmans, Göran Hutchinson, Amy Hunter, David J. Jenab, Mazda Jiang, Guoliang Khaw, Kay-Tee LaCroix, Andrea Li, Zhaoshen Mendelsohn, Julie B. Panico, Salvatore Patel, Alpa V. Qian, Zhirong Sesso, Howard D. Shen, Hongbing Shu, Xiao-Ou Tjønneland, Anne Tobias, Geoffrey S. Trichopoulos, Dimitrios Virtamo, Jarmo Visvanathan, Kala Wactawski-Wende, Jean Wang, Chengfeng Yu, Kai Zeleniuch-Jacquotte, Anne Chanock, Stephen J. Hoover, Robert N. Hartge, Patricia Fuchs, Charles S. Lin, Dongxin Wolpin, Brian M. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Càncer de pàncrees Polimorfisme genètic Pancreas cancer Genetic polymorphisms |
| topic |
Càncer de pàncrees Polimorfisme genètic Pancreas cancer Genetic polymorphisms |
| description |
Background and objective: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). Results: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63x10(-7)), rs981621 (p=1.65x10(-7)) and rs16861827 (p=3.75x10(-7)), respectively. 131 SNPs with p10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72x10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Conclusions: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/124211 |
| url |
https://hdl.handle.net/2445/124211 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Versió postprint del document publicat a: https://doi.org/10.1136/gutjnl-2012-303477 Gut, 2014, vol. 63, num. 1 https://doi.org/10.1136/gutjnl-2012-303477 |
| dc.rights.none.fl_str_mv |
(c) BMJ Publishing Group Ltd; British Society of Gastroenterology, 2014 info:eu-repo/semantics/openAccess |
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(c) BMJ Publishing Group Ltd; British Society of Gastroenterology, 2014 |
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openAccess |
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application/pdf |
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BMJ Publishing Group |
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BMJ Publishing Group |
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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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1869411807484968960 |
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15.301603 |