Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer
Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806...
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Tipo de documento: | Artigo |
| Estado: | Published version |
| Data de publicação: | 2024 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositório: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/214828 |
| Acesso em linha: | https://hdl.handle.net/2445/214828 |
| Nível de acesso: | Acesso aberto |
| Palavra-chave: | Càncer colorectal Farmacogenètica Colorectal cancer Pharmacogenetics |
| _version_ | 1878740342592765952 |
|---|---|
| author | Drew, David A. |
| author2 | Kim, Andre E. Lin, Yi Qu, Conghui Morrison, John Lewinger, Juan Pablo Kawaguchi, Eric Wang, Jun Fu, Yubo Zemlianskaia, Natalia Díez Obrero, Virginia Bien, Stephanie A. Dimou, Niki Albanes, Demetrius Baurley, James W. Wu, Anna H. Buchanan, Daniel D. Potter, John D. Prentice, Ross L. Harlid, Sophia Arndt, Volker Barry, Elizabeth L. Berndt, Sonja I. Bouras, Emmanouil Brenner, Hermann Budiarto, Arif Burnett Hartman, Andrea Campbell, Peter T. Carreras Torres, Robert Casey, Graham Chang Claude, Jenny Conti, David V. Devall, Matthew A. M. Figueiredo, Jane C. Gruber, Stephen B. Gsur, Andrea Gunter, Marc J. Harrison, Tabitha A. Hidaka, Akihisa Hoffmeister, Michael Huyghe, Jeroen R. Jenkins, Mark A. Jordahl, Kristina M. Kundaje, Anshul Le Marchand, Loic Li, Li Lynch, Brigid M. Murphy, Neil Nassir, Rami Newcomb, Polly A. Newton, Christina C. Obón Santacana, Mireia Ogino, Shuji Ose, Jennifer Pai, Rish K. Palmer, Julie R. Papadimitriou, Nikos Pardamean, Bens Pellatt, Andrew J. Peoples, Anita R. Platz, Elizabeth A. Rennert, Gad Ruiz Narvaez, Edward Sakoda, Lori C. Scacheri, Peter C. Schmit, Stephanie L. Schoen, Robert E. Stern, Mariana C. Su, Yu-ru Thomas, Duncan C. Tian, Yu Tsilidis, Konstantinos K. Ulrich, Cornelia M. Um, Caroline Y. Van Duijnhoven, Fränzel J. B. Van Guelpen, Bethany White, Emily Hsu, Li Moreno Aguado, Víctor Peters, Ulrike Chan, Andrew T. Gauderman, W. James |
| 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 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_browse | Albanes, Demetrius Arndt, Volker Barry, Elizabeth L. Baurley, James W. Berndt, Sonja I. Bien, Stephanie A. Bouras, Emmanouil Brenner, Hermann Buchanan, Daniel D. Budiarto, Arif Burnett Hartman, Andrea Campbell, Peter T. Carreras Torres, Robert Casey, Graham Chan, Andrew T. Chang Claude, Jenny Conti, David V. Devall, Matthew A. M. Dimou, Niki Drew, David A. Díez Obrero, Virginia Figueiredo, Jane C. Fu, Yubo Gauderman, W. James Gruber, Stephen B. Gsur, Andrea Gunter, Marc J. Harlid, Sophia Harrison, Tabitha A. Hidaka, Akihisa Hoffmeister, Michael Hsu, Li Huyghe, Jeroen R. Jenkins, Mark A. Jordahl, Kristina M. Kawaguchi, Eric Kim, Andre E. Kundaje, Anshul Le Marchand, Loic Lewinger, Juan Pablo Li, Li Lin, Yi Lynch, Brigid M. Moreno Aguado, Víctor Morrison, John Murphy, Neil Nassir, Rami Newcomb, Polly A. Newton, Christina C. Obón Santacana, Mireia Ogino, Shuji Ose, Jennifer Pai, Rish K. Palmer, Julie R. Papadimitriou, Nikos Pardamean, Bens Pellatt, Andrew J. Peoples, Anita R. Peters, Ulrike Platz, Elizabeth A. Potter, John D. Prentice, Ross L. Qu, Conghui Rennert, Gad Ruiz Narvaez, Edward Sakoda, Lori C. Scacheri, Peter C. Schmit, Stephanie L. Schoen, Robert E. Stern, Mariana C. Su, Yu-ru Thomas, Duncan C. Tian, Yu Tsilidis, Konstantinos K. Ulrich, Cornelia M. Um, Caroline Y. Van Duijnhoven, Fränzel J. B. Van Guelpen, Bethany Wang, Jun White, Emily Wu, Anna H. Zemlianskaia, Natalia |
| author_facet | Drew, David A. Kim, Andre E. Lin, Yi Qu, Conghui Morrison, John Lewinger, Juan Pablo Kawaguchi, Eric Wang, Jun Fu, Yubo Zemlianskaia, Natalia Díez Obrero, Virginia Bien, Stephanie A. Dimou, Niki Albanes, Demetrius Baurley, James W. Wu, Anna H. Buchanan, Daniel D. Potter, John D. Prentice, Ross L. Harlid, Sophia Arndt, Volker Barry, Elizabeth L. Berndt, Sonja I. Bouras, Emmanouil Brenner, Hermann Budiarto, Arif Burnett Hartman, Andrea Campbell, Peter T. Carreras Torres, Robert Casey, Graham Chang Claude, Jenny Conti, David V. Devall, Matthew A. M. Figueiredo, Jane C. Gruber, Stephen B. Gsur, Andrea Gunter, Marc J. Harrison, Tabitha A. Hidaka, Akihisa Hoffmeister, Michael Huyghe, Jeroen R. Jenkins, Mark A. Jordahl, Kristina M. Kundaje, Anshul Le Marchand, Loic Li, Li Lynch, Brigid M. Murphy, Neil Nassir, Rami Newcomb, Polly A. Newton, Christina C. Obón Santacana, Mireia Ogino, Shuji Ose, Jennifer Pai, Rish K. Palmer, Julie R. Papadimitriou, Nikos Pardamean, Bens Pellatt, Andrew J. Peoples, Anita R. Platz, Elizabeth A. Rennert, Gad Ruiz Narvaez, Edward Sakoda, Lori C. Scacheri, Peter C. Schmit, Stephanie L. Schoen, Robert E. Stern, Mariana C. Su, Yu-ru Thomas, Duncan C. Tian, Yu Tsilidis, Konstantinos K. Ulrich, Cornelia M. Um, Caroline Y. Van Duijnhoven, Fränzel J. B. Van Guelpen, Bethany White, Emily Hsu, Li Moreno Aguado, Víctor Peters, Ulrike Chan, Andrew T. Gauderman, W. James |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_d14d5e1d2771d070941dade3a43d9486 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/214828 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | American Association for the Advancement of Science (AAAS) |
| publisherStr | American Association for the Advancement of Science (AAAS) |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer Drew, David A. Kim, Andre E. Lin, Yi Qu, Conghui Morrison, John Lewinger, Juan Pablo Kawaguchi, Eric Wang, Jun Fu, Yubo Zemlianskaia, Natalia Díez Obrero, Virginia Bien, Stephanie A. Dimou, Niki Albanes, Demetrius Baurley, James W. Wu, Anna H. Buchanan, Daniel D. Potter, John D. Prentice, Ross L. Harlid, Sophia Arndt, Volker Barry, Elizabeth L. Berndt, Sonja I. Bouras, Emmanouil Brenner, Hermann Budiarto, Arif Burnett Hartman, Andrea Campbell, Peter T. Carreras Torres, Robert Casey, Graham Chang Claude, Jenny Conti, David V. Devall, Matthew A. M. Figueiredo, Jane C. Gruber, Stephen B. Gsur, Andrea Gunter, Marc J. Harrison, Tabitha A. Hidaka, Akihisa Hoffmeister, Michael Huyghe, Jeroen R. Jenkins, Mark A. Jordahl, Kristina M. Kundaje, Anshul Le Marchand, Loic Li, Li Lynch, Brigid M. Murphy, Neil Nassir, Rami Newcomb, Polly A. Newton, Christina C. Obón Santacana, Mireia Ogino, Shuji Ose, Jennifer Pai, Rish K. Palmer, Julie R. Papadimitriou, Nikos Pardamean, Bens Pellatt, Andrew J. Peoples, Anita R. Platz, Elizabeth A. Rennert, Gad Ruiz Narvaez, Edward Sakoda, Lori C. Scacheri, Peter C. Schmit, Stephanie L. Schoen, Robert E. Stern, Mariana C. Su, Yu-ru Thomas, Duncan C. Tian, Yu Tsilidis, Konstantinos K. Ulrich, Cornelia M. Um, Caroline Y. Van Duijnhoven, Fränzel J. B. Van Guelpen, Bethany White, Emily Hsu, Li Moreno Aguado, Víctor Peters, Ulrike Chan, Andrew T. Gauderman, W. James Càncer colorectal Farmacogenètica Colorectal cancer Pharmacogenetics Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation. American Association for the Advancement of Science (AAAS) https://hdl.handle.net/2445/214828 |
| spellingShingle | Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer Drew, David A. Càncer colorectal Farmacogenètica Colorectal cancer Pharmacogenetics |
| status_str | publishedVersion |
| title | Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer |
| title_full | Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer |
| title_fullStr | Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer |
| title_full_unstemmed | Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer |
| title_short | Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer |
| title_sort | Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer |
| topic | Càncer colorectal Farmacogenètica Colorectal cancer Pharmacogenetics |
| topic_facet | Càncer colorectal Farmacogenètica Colorectal cancer Pharmacogenetics |
| url | https://hdl.handle.net/2445/214828 |