Mendelian randomization analysis of C-reactive protein on colorectal cancer risk

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

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...

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Authors:	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
Format:	article
Status:	Versión aceptada para publicación
Publication Date:	2019
Country:	España
Institution:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/174894
Online Access:	https://hdl.handle.net/2445/174894
Access Level:	Open access
Keyword:	Proteïnes Càncer colorectal Epidemiologia genètica Factors de risc en les malalties Proteins Colorectal cancer Genetic epidemiology Risk factors in diseases

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repository_id_str
spelling	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 Press2021202120192021info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion14 p.application/pdfhttps://hdl.handle.net/2445/174894Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió 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:recercat.cat:2445/1748942026-05-29T05:05:01Z
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 2021 2021 2021
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
url	https://hdl.handle.net/2445/174894
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/10.1093/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
rights_invalid_str_mv	(c) Wang, Xiaoliang et al., 2019
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	14 p. application/pdf
dc.publisher.none.fl_str_mv	Oxford University Press
publisher.none.fl_str_mv	Oxford University Press
dc.source.none.fl_str_mv	Articles publicats en revistes (Ciències Clíniques) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15.812429

Mendelian randomization analysis of C-reactive protein on colorectal cancer risk

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