Drew DAKim AELin YQu CMorrison JLewinger JPKawaguchi EWang JFu YZemlianskaia NDíez-Obrero VBien SADimou NAlbanes DBaurley JWWu AHBuchanan DDPotter JDPrentice RLHarlid SArndt VBarry ELBerndt SIBouras EBrenner HBudiarto ABurnett-Hartman ACampbell PTCarreras-Torres RCasey GChang-Claude JConti DVDevall MAMFigueiredo JCGruber SBGsur AGunter MJHarrison TAHidaka AHoffmeister MHuyghe JRJenkins MAJordahl KMKundaje ALe Marchand LLi LLynch BMMurphy NNassir RNewcomb PANewton CCObón-Santacana MOgino SOse JPai RKPalmer JRPapadimitriou NPardamean BPellatt AJPeoples ARPlatz EARennert GRuiz-Narvaez ESakoda LCScacheri PCSchmit SLSchoen REStern MCSu Y-RThomas DCTian YTsilidis KKUlrich CMUm CYvan Duijnhoven FJBVan Guelpen BWhite EHsu LMoreno VPeters UChan ATGauderman WJ2024-07-212024-07-212024-05-29Drew DA, Kim AE, Lin Y, Qu C, Morrison J, Lewinger JP, Kawaguchi E, Wang J, Fu Y, Zemlianskaia N, Díez-Obrero V, Bien SA, Dimou N, Albanes D, Baurley JW, Wu AH, Buchanan DD, Potter JD, Prentice RL, Harlid S, Arndt V, Barry EL, Berndt SI, Bouras E, Brenner H, Budiarto A, Burnett-Hartman A, Campbell PT, Carreras-Torres R, Casey G, Chang-Claude J, Conti DV, Devall MAM, Figueiredo JC, Gruber SB, Gsur A, Gunter MJ, Harrison TA, Hidaka A, Hoffmeister M, Huyghe JR, Jenkins MA, Jordahl KM, Kundaje A, Le Marchand L, Li L, Lynch BM, Murphy N, Nassir R, Newcomb PA, Newton CC, Obón-Santacana M, Ogino S, Ose J, Pai RK, Palmer JR, Papadimitriou N, Pardamean B, Pellatt AJ, Peoples AR, Platz EA, Rennert G, Ruiz-Narvaez E, Sakoda LC, Scacheri PC, Schmit SL, Schoen RE, Stern MC, Su Y-R, Thomas DC, Tian Y, Tsilidis KK, Ulrich CM, Um CY, van Duijnhoven FJB, Van Guelpen B, White E, Hsu L, Moreno V, Peters U, Chan AT, Gauderman WJ. (2024). Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer.. Sci Adv. 10. 22. (pp. eadk3121-).2375-2548https://mro.massey.ac.nz/handle/10179/70248Regular, 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.(c) 2024 The Author/sCC BY 4.0https://creativecommons.org/licenses/by/4.0/HumansColorectal NeoplasmsAnti-Inflammatory Agents, Non-SteroidalGenome-Wide Association StudyPolymorphism, Single NucleotideAspirinReceptors, Prostaglandin E, EP4 SubtypeMaleGenetic Predisposition to DiseaseFemaleCase-Control StudiesMiddle AgedGenetic LociAgedJournal article10.1126/sciadv.adk31212375-2548journal-articleeadk3121-https://www.ncbi.nlm.nih.gov/pubmed/38809988