biostudies-literatureNounu ACancer Research UKNCATS NIH HHSNIA NIH HHSNIEHS NIH HHSRegional Council of Pays de la LoireNHLBI NIH HHSNational Institute on AgingEuropean Research CouncilU.S. Department of Health and Human ServicesOntario Research FundNIH HHSWHI NIH HHSIntramural NIH HHSUK Medical Research Council Integrative Epidemiology UnitWorld Health OrganizationNIHThe Johns Hopkins UniversityEarly Detection Research NetworkNCINIDDK NIH HHSMedical Research CouncilBowel Cancer UKNHGRI NIH HHSNCI NIH HHSMRC ResearchHospital Clinical Research ProgramWellcome Trust564-575https://www.ebi.ac.uk/biostudies/studies/S-EPMC8086774biostudies-literatureUnknown30(3)<h4>Background</h4>Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.<h4>Methods</h4>Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (<i>N</i> = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (<i>N</i> = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive OncologyA Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer.PMC8086774U01 CA13708819PT0039K05 CA154337U01 CA074783K05 CA152715R01 CA143247C18281/A19169;HHSN268201100001IR01 CA072520R37 CA054281HHSN268201100001CU01 HG004438MC_UU_12013_2U01 CA122839R01 CA081488R01 CA81488P01 CA033619P30 CA016058001MR/R017247/1;HHSN268201100002IR01 CA136726HHSN268201100002CC18281/A1916919169U01 CA084968U24 CA07478319167K07 CA190673HHSN268201100003CHHSN268201700006CMC_UU_12013/2UM1 CA167552U01 CA067941P30 DK034987S10 OD028685P01 CA055075U01 CA86308HHSN268201100003IR01 CA059045232997U01 CA164930U19 CA148107U24 CA07479429019HHSN268201100004CR01 CA066635R03 CA153323217487/Z/19/ZR01201407HHSN268201100004IUM1 CA18288311975U01 AG018033P01 CA087969R01 CA197350KL2 TR000421R21 CA191312P30 CA014089R01 CA151993P30 CA076292R01 CA07636616561P30 CA006973G1000143R01 CA207371R01 CA13717819PT0039;R01 CA042182217487/Z/19/Z;R01 CA063464R01 CA067941P50 CA127003MR/R017247/1HHSN268201100046CUM1 CA186107112746U01 CA086308R35 CA197735U01 AG18033U01 HG004446P30 CA008748U01 CA167552R01 CA048998T32 ES013678U01 CA167551R01 CA189184Z01 CP010200HHSN268201200008IC19/A11975;R01 CA097325HHSN268201200008CMC_UU_00011/4U01 CA164973R01 CA201407P30 CA015704U01 CA074794U01 CA206110HHSN271201100004CPHRC-BRD09/CU10 CA037429Richmond RCBishop DTBermejo JLLin YBerndt SISchoen REPharoah PDPLe Marchand LCastellvi-Bel SLi CIPeters USlattery MLUlrich CMGunter MJWolk ABaron JAChang-Claude JGreenhough ARelton CLZheng WVan Guelpen BKweon SSLi LScherer DFigueiredo JCGruber SBvan Duijnhoven FJBBrenner HGsur ASakoda LCHoffmeister MHeesom KJWoods MODrew DAWilliams ACPlatz EAWeinstein SJZheng JKeku TOSchafmayer CGallinger SGiles GGWhite ECasey GNewcomb PABuchanan DDStadler ZKHampel HChan ATLindor NMNounu AVodicka PLindblom AKim HRRennert GAlbanes DHopper JLHarrison TACampbell PTMoreno VVodickova LWu AHfalseA Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer.<h4>Background</h4>Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.<h4>Methods</h4>Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (<i>N</i> = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (<i>N</i> = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was 2021-01-01T00:00:00Z2021 Mar2026-05-09T00:39:12.302Z2022-02-11T10:05:09.46ZS-EPMC80867743331802910.1158/1055-9965.epi-20-117610.1158/1055-9965.EPI-20-1176