Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk
Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/174066 |
| Acceso en línea: | https://hdl.handle.net/2445/174066 |
| Access Level: | acceso abierto |
| Palabra clave: | Càncer colorectal Factors de risc en les malalties Colorectal cancer Risk factors in diseases |
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Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer riskKhankari, Nikhil K.Banbury, Barbara L.Borges, Maria C.Haycock, PhilipAlbanes, DemetriusArndt, VolkerBerndt, Sonja I.Bézieau, StéphaneBrenner, HermannCampbell, Peter T.Casey, GrahamChan, Andrew T.Chang Claude, JennyConti, David V.Cotterchio, MichelleEnglish, Dallas R.Figueiredo, Jane C.Giles, Graham G.Giovannucci, Edward L.Gunter, Marc J.Hampe, JochenHoffmeister, MichaelHopper, John L.Jenkins, Mark A.Joshi, Amit D.Marchand, Loïc LeLemire, MathieuLi, Christopher I.Li, LiLindblom, AnnikaMartín Sánchez, VicenteMoreno Aguado, VíctorNewcomb, Polly A.Offit, KennethPharoah, Paul D. P.Rennert, GadSakoda, Lori C.Schafmayer, ClemensSchmit, Stephanie L.Slattery, Martha L.Song, MingyangThibodeau, Stephen N.Ulrich, Cornelia M.Weinstein, Stephanie J.White, EmilyWin, Aung KoWolk, AlicjaWoods, Michael O.Wu, Anna H.Cai, QiuyinDenny, Joshua C.Edwards, Todd L.Murff, Harvey J.Gruber, Stephen B.Peters, UlrikeZheng, WeiCàncer colorectalFactors de risc en les malaltiesColorectal cancerRisk factors in diseasesBackground: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.American Association for Cancer Research (AACR)2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/174066Articles 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/10.1158/1055-9965.EPI-19-0891Cancer Epidemiology Biomarkers & Prevention, 2020, vol. 29, issue. 4, p. 860-870https://doi.org/10.1158/1055-9965.EPI-19-0891(c) American Association for Cancer Research (AACR), 2020info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1740662026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk |
| title |
Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk |
| spellingShingle |
Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk Khankari, Nikhil K. Càncer colorectal Factors de risc en les malalties Colorectal cancer Risk factors in diseases |
| title_short |
Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk |
| title_full |
Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk |
| title_fullStr |
Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk |
| title_full_unstemmed |
Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk |
| title_sort |
Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk |
| dc.creator.none.fl_str_mv |
Khankari, Nikhil K. Banbury, Barbara L. Borges, Maria C. Haycock, Philip Albanes, Demetrius Arndt, Volker Berndt, Sonja I. Bézieau, Stéphane Brenner, Hermann Campbell, Peter T. Casey, Graham Chan, Andrew T. Chang Claude, Jenny Conti, David V. Cotterchio, Michelle English, Dallas R. Figueiredo, Jane C. Giles, Graham G. Giovannucci, Edward L. Gunter, Marc J. Hampe, Jochen Hoffmeister, Michael Hopper, John L. Jenkins, Mark A. Joshi, Amit D. Marchand, Loïc Le Lemire, Mathieu Li, Christopher I. Li, Li Lindblom, Annika Martín Sánchez, Vicente Moreno Aguado, Víctor Newcomb, Polly A. Offit, Kenneth Pharoah, Paul D. P. Rennert, Gad Sakoda, Lori C. Schafmayer, Clemens Schmit, Stephanie L. Slattery, Martha L. Song, Mingyang Thibodeau, Stephen N. Ulrich, Cornelia M. Weinstein, Stephanie J. White, Emily Win, Aung Ko Wolk, Alicja Woods, Michael O. Wu, Anna H. Cai, Qiuyin Denny, Joshua C. Edwards, Todd L. Murff, Harvey J. Gruber, Stephen B. Peters, Ulrike Zheng, Wei |
| author |
Khankari, Nikhil K. |
| author_facet |
Khankari, Nikhil K. Banbury, Barbara L. Borges, Maria C. Haycock, Philip Albanes, Demetrius Arndt, Volker Berndt, Sonja I. Bézieau, Stéphane Brenner, Hermann Campbell, Peter T. Casey, Graham Chan, Andrew T. Chang Claude, Jenny Conti, David V. Cotterchio, Michelle English, Dallas R. Figueiredo, Jane C. Giles, Graham G. Giovannucci, Edward L. Gunter, Marc J. Hampe, Jochen Hoffmeister, Michael Hopper, John L. Jenkins, Mark A. Joshi, Amit D. Marchand, Loïc Le Lemire, Mathieu Li, Christopher I. Li, Li Lindblom, Annika Martín Sánchez, Vicente Moreno Aguado, Víctor Newcomb, Polly A. Offit, Kenneth Pharoah, Paul D. P. Rennert, Gad Sakoda, Lori C. Schafmayer, Clemens Schmit, Stephanie L. Slattery, Martha L. Song, Mingyang Thibodeau, Stephen N. Ulrich, Cornelia M. Weinstein, Stephanie J. White, Emily Win, Aung Ko Wolk, Alicja Woods, Michael O. Wu, Anna H. Cai, Qiuyin Denny, Joshua C. Edwards, Todd L. Murff, Harvey J. Gruber, Stephen B. Peters, Ulrike Zheng, Wei |
| author_role |
author |
| author2 |
Banbury, Barbara L. Borges, Maria C. Haycock, Philip Albanes, Demetrius Arndt, Volker Berndt, Sonja I. Bézieau, Stéphane Brenner, Hermann Campbell, Peter T. Casey, Graham Chan, Andrew T. Chang Claude, Jenny Conti, David V. Cotterchio, Michelle English, Dallas R. Figueiredo, Jane C. Giles, Graham G. Giovannucci, Edward L. Gunter, Marc J. Hampe, Jochen Hoffmeister, Michael Hopper, John L. Jenkins, Mark A. Joshi, Amit D. Marchand, Loïc Le Lemire, Mathieu Li, Christopher I. Li, Li Lindblom, Annika Martín Sánchez, Vicente Moreno Aguado, Víctor Newcomb, Polly A. Offit, Kenneth Pharoah, Paul D. P. Rennert, Gad Sakoda, Lori C. Schafmayer, Clemens Schmit, Stephanie L. Slattery, Martha L. Song, Mingyang Thibodeau, Stephen N. Ulrich, Cornelia M. Weinstein, Stephanie J. White, Emily Win, Aung Ko Wolk, Alicja Woods, Michael O. Wu, Anna H. Cai, Qiuyin Denny, Joshua C. Edwards, Todd L. Murff, Harvey J. Gruber, Stephen B. Peters, Ulrike Zheng, Wei |
| 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 |
Càncer colorectal Factors de risc en les malalties Colorectal cancer Risk factors in diseases |
| topic |
Càncer colorectal Factors de risc en les malalties Colorectal cancer Risk factors in diseases |
| description |
Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 |
| 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/2445/174066 |
| url |
https://hdl.handle.net/2445/174066 |
| 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/10.1158/1055-9965.EPI-19-0891 Cancer Epidemiology Biomarkers & Prevention, 2020, vol. 29, issue. 4, p. 860-870 https://doi.org/10.1158/1055-9965.EPI-19-0891 |
| dc.rights.none.fl_str_mv |
(c) American Association for Cancer Research (AACR), 2020 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) American Association for Cancer Research (AACR), 2020 |
| eu_rights_str_mv |
openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
American Association for Cancer Research (AACR) |
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American Association for Cancer Research (AACR) |
| dc.source.none.fl_str_mv |
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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15,300724 |