Mendelian randomization analysis of C-reactive protein on colorectal cancer risk
Background: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versión aceptada para publicación |
| Data de publicação: | 2019 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositório: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/174894 |
| Acesso em linha: | https://hdl.handle.net/2445/174894 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Proteïnes Càncer colorectal Epidemiologia genètica Factors de risc en les malalties Proteins Colorectal cancer Genetic epidemiology Risk factors in diseases |
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Mendelian randomization analysis of C-reactive protein on colorectal cancer riskWang, XiaoliangDai, James Y.Albanes, DemetriusArndt, VolkerBerndt, Sonja I.Bézieau, StéphaneBrenner, HermannBuchanan, Daniel D.Butterbach, KatjaCaan, Bette J.Casey, GrahamCampbell, Peter T.Chan, Andrew T.Chen, ZhengyiChang Claude, JennyCotterchio, MichelleEaston, Douglas F.Giles, Graham G.Giovannucci, EdwardGrady, William M.Hoffmeister, MichaelHopper, John L.Hsu, LiJenkins, Mark A.Joshi, Amit D.Lampe, Johanna W.Larsson, Susanna C.Lejbkowicz, FlavioLi, LiLindblom, AnnikaLe Marchand, LoicMartín Sánchez, VicenteMilne, Roger L.Moreno Aguado, VíctorNewcomb, Polly A.Offit, KennethOgino, ShujiPharoah, Paul D. P.Pinchev, MilaPotter, John D.Rennert, Hedy S.Rennert, GadSaliba, WalidSchafmayer, ClemensSchoen, Robert E.Schrotz King, PetraSlattery, Martha L.Song, MingyangStegmaier, ChristaWeinstein, Stephanie J.Wolk, AlicjaWoods, Michael O.Wu, Anna H.Gruber, Stephen B.Peters, UlrikeWhite, EmilyProteïnesCàncer colorectalEpidemiologia genèticaFactors de risc en les malaltiesProteinsColorectal cancerGenetic epidemiologyRisk factors in diseasesBackground: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. Methods: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. Results: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. Conclusions: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.Oxford University Press2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/174894Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1093/ije/dyy244International Journal of Epidemiology, 2019, vol. 48, num. 3, p. 767-780https://doi.org/10.1093/ije/dyy244(c) Wang, Xiaoliang et al., 2019info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1748942026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Mendelian randomization analysis of C-reactive protein on colorectal cancer risk |
| title |
Mendelian randomization analysis of C-reactive protein on colorectal cancer risk |
| spellingShingle |
Mendelian randomization analysis of C-reactive protein on colorectal cancer risk Wang, Xiaoliang Proteïnes Càncer colorectal Epidemiologia genètica Factors de risc en les malalties Proteins Colorectal cancer Genetic epidemiology Risk factors in diseases |
| title_short |
Mendelian randomization analysis of C-reactive protein on colorectal cancer risk |
| title_full |
Mendelian randomization analysis of C-reactive protein on colorectal cancer risk |
| title_fullStr |
Mendelian randomization analysis of C-reactive protein on colorectal cancer risk |
| title_full_unstemmed |
Mendelian randomization analysis of C-reactive protein on colorectal cancer risk |
| title_sort |
Mendelian randomization analysis of C-reactive protein on colorectal cancer risk |
| dc.creator.none.fl_str_mv |
Wang, Xiaoliang Dai, James Y. Albanes, Demetrius Arndt, Volker Berndt, Sonja I. Bézieau, Stéphane Brenner, Hermann Buchanan, Daniel D. Butterbach, Katja Caan, Bette J. Casey, Graham Campbell, Peter T. Chan, Andrew T. Chen, Zhengyi Chang Claude, Jenny Cotterchio, Michelle Easton, Douglas F. Giles, Graham G. Giovannucci, Edward Grady, William M. Hoffmeister, Michael Hopper, John L. Hsu, Li Jenkins, Mark A. Joshi, Amit D. Lampe, Johanna W. Larsson, Susanna C. Lejbkowicz, Flavio Li, Li Lindblom, Annika Le Marchand, Loic Martín Sánchez, Vicente Milne, Roger L. Moreno Aguado, Víctor Newcomb, Polly A. Offit, Kenneth Ogino, Shuji Pharoah, Paul D. P. Pinchev, Mila Potter, John D. Rennert, Hedy S. Rennert, Gad Saliba, Walid Schafmayer, Clemens Schoen, Robert E. Schrotz King, Petra Slattery, Martha L. Song, Mingyang Stegmaier, Christa Weinstein, Stephanie J. Wolk, Alicja Woods, Michael O. Wu, Anna H. Gruber, Stephen B. Peters, Ulrike White, Emily |
| author |
Wang, Xiaoliang |
| author_facet |
Wang, Xiaoliang Dai, James Y. Albanes, Demetrius Arndt, Volker Berndt, Sonja I. Bézieau, Stéphane Brenner, Hermann Buchanan, Daniel D. Butterbach, Katja Caan, Bette J. Casey, Graham Campbell, Peter T. Chan, Andrew T. Chen, Zhengyi Chang Claude, Jenny Cotterchio, Michelle Easton, Douglas F. Giles, Graham G. Giovannucci, Edward Grady, William M. Hoffmeister, Michael Hopper, John L. Hsu, Li Jenkins, Mark A. Joshi, Amit D. Lampe, Johanna W. Larsson, Susanna C. Lejbkowicz, Flavio Li, Li Lindblom, Annika Le Marchand, Loic Martín Sánchez, Vicente Milne, Roger L. Moreno Aguado, Víctor Newcomb, Polly A. Offit, Kenneth Ogino, Shuji Pharoah, Paul D. P. Pinchev, Mila Potter, John D. Rennert, Hedy S. Rennert, Gad Saliba, Walid Schafmayer, Clemens Schoen, Robert E. Schrotz King, Petra Slattery, Martha L. Song, Mingyang Stegmaier, Christa Weinstein, Stephanie J. Wolk, Alicja Woods, Michael O. Wu, Anna H. Gruber, Stephen B. Peters, Ulrike White, Emily |
| author_role |
author |
| author2 |
Dai, James Y. Albanes, Demetrius Arndt, Volker Berndt, Sonja I. Bézieau, Stéphane Brenner, Hermann Buchanan, Daniel D. Butterbach, Katja Caan, Bette J. Casey, Graham Campbell, Peter T. Chan, Andrew T. Chen, Zhengyi Chang Claude, Jenny Cotterchio, Michelle Easton, Douglas F. Giles, Graham G. Giovannucci, Edward Grady, William M. Hoffmeister, Michael Hopper, John L. Hsu, Li Jenkins, Mark A. Joshi, Amit D. Lampe, Johanna W. Larsson, Susanna C. Lejbkowicz, Flavio Li, Li Lindblom, Annika Le Marchand, Loic Martín Sánchez, Vicente Milne, Roger L. Moreno Aguado, Víctor Newcomb, Polly A. Offit, Kenneth Ogino, Shuji Pharoah, Paul D. P. Pinchev, Mila Potter, John D. Rennert, Hedy S. Rennert, Gad Saliba, Walid Schafmayer, Clemens Schoen, Robert E. Schrotz King, Petra Slattery, Martha L. Song, Mingyang Stegmaier, Christa Weinstein, Stephanie J. Wolk, Alicja Woods, Michael O. Wu, Anna H. Gruber, Stephen B. Peters, Ulrike White, Emily |
| 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 |
| dc.subject.none.fl_str_mv |
Proteïnes Càncer colorectal Epidemiologia genètica Factors de risc en les malalties Proteins Colorectal cancer Genetic epidemiology Risk factors in diseases |
| topic |
Proteïnes Càncer colorectal Epidemiologia genètica Factors de risc en les malalties Proteins Colorectal cancer Genetic epidemiology Risk factors in diseases |
| description |
Background: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. Methods: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. Results: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. Conclusions: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 |
| 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/2445/174894 |
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https://hdl.handle.net/2445/174894 |
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Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Versió postprint del document publicat a: https://doi.org/10.1093/ije/dyy244 International Journal of Epidemiology, 2019, vol. 48, num. 3, p. 767-780 https://doi.org/10.1093/ije/dyy244 |
| dc.rights.none.fl_str_mv |
(c) Wang, Xiaoliang et al., 2019 info:eu-repo/semantics/openAccess |
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(c) Wang, Xiaoliang et al., 2019 |
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openAccess |
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application/pdf |
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Oxford University Press |
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Oxford University Press |
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Articles publicats en revistes (Ciències Clíniques) 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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1869405521617879040 |
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15,301603 |