Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer.

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dc.citation.issue22
dc.citation.volume10
dc.contributor.authorDrew DA
dc.contributor.authorKim AE
dc.contributor.authorLin Y
dc.contributor.authorQu C
dc.contributor.authorMorrison J
dc.contributor.authorLewinger JP
dc.contributor.authorKawaguchi E
dc.contributor.authorWang J
dc.contributor.authorFu Y
dc.contributor.authorZemlianskaia N
dc.contributor.authorDíez-Obrero V
dc.contributor.authorBien SA
dc.contributor.authorDimou N
dc.contributor.authorAlbanes D
dc.contributor.authorBaurley JW
dc.contributor.authorWu AH
dc.contributor.authorBuchanan DD
dc.contributor.authorPotter JD
dc.contributor.authorPrentice RL
dc.contributor.authorHarlid S
dc.contributor.authorArndt V
dc.contributor.authorBarry EL
dc.contributor.authorBerndt SI
dc.contributor.authorBouras E
dc.contributor.authorBrenner H
dc.contributor.authorBudiarto A
dc.contributor.authorBurnett-Hartman A
dc.contributor.authorCampbell PT
dc.contributor.authorCarreras-Torres R
dc.contributor.authorCasey G
dc.contributor.authorChang-Claude J
dc.contributor.authorConti DV
dc.contributor.authorDevall MAM
dc.contributor.authorFigueiredo JC
dc.contributor.authorGruber SB
dc.contributor.authorGsur A
dc.contributor.authorGunter MJ
dc.contributor.authorHarrison TA
dc.contributor.authorHidaka A
dc.contributor.authorHoffmeister M
dc.contributor.authorHuyghe JR
dc.contributor.authorJenkins MA
dc.contributor.authorJordahl KM
dc.contributor.authorKundaje A
dc.contributor.authorLe Marchand L
dc.contributor.authorLi L
dc.contributor.authorLynch BM
dc.contributor.authorMurphy N
dc.contributor.authorNassir R
dc.contributor.authorNewcomb PA
dc.contributor.authorNewton CC
dc.contributor.authorObón-Santacana M
dc.contributor.authorOgino S
dc.contributor.authorOse J
dc.contributor.authorPai RK
dc.contributor.authorPalmer JR
dc.contributor.authorPapadimitriou N
dc.contributor.authorPardamean B
dc.contributor.authorPellatt AJ
dc.contributor.authorPeoples AR
dc.contributor.authorPlatz EA
dc.contributor.authorRennert G
dc.contributor.authorRuiz-Narvaez E
dc.contributor.authorSakoda LC
dc.contributor.authorScacheri PC
dc.contributor.authorSchmit SL
dc.contributor.authorSchoen RE
dc.contributor.authorStern MC
dc.contributor.authorSu Y-R
dc.contributor.authorThomas DC
dc.contributor.authorTian Y
dc.contributor.authorTsilidis KK
dc.contributor.authorUlrich CM
dc.contributor.authorUm CY
dc.contributor.authorvan Duijnhoven FJB
dc.contributor.authorVan Guelpen B
dc.contributor.authorWhite E
dc.contributor.authorHsu L
dc.contributor.authorMoreno V
dc.contributor.authorPeters U
dc.contributor.authorChan AT
dc.contributor.authorGauderman WJ
dc.coverage.spatialUnited States
dc.date.accessioned2024-07-21T23:08:53Z
dc.date.available2024-07-21T23:08:53Z
dc.date.issued2024-05-29
dc.description.abstractRegular, 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.
dc.description.confidentialfalse
dc.edition.editionMay 2024
dc.format.paginationeadk3121-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/38809988
dc.identifier.citationDrew 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-).
dc.identifier.doi10.1126/sciadv.adk3121
dc.identifier.eissn2375-2548
dc.identifier.elements-typejournal-article
dc.identifier.issn2375-2548
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/70248
dc.languageeng
dc.publisherAmerican Association for the Advancement of Science
dc.publisher.urihttps://www.science.org/doi/10.1126/sciadv.adk3121
dc.relation.isPartOfSci Adv
dc.rights(c) 2024 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectAnti-Inflammatory Agents, Non-Steroidal
dc.subjectGenome-Wide Association Study
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAspirin
dc.subjectReceptors, Prostaglandin E, EP4 Subtype
dc.subjectMale
dc.subjectGenetic Predisposition to Disease
dc.subjectFemale
dc.subjectCase-Control Studies
dc.subjectMiddle Aged
dc.subjectGenetic Loci
dc.subjectAged
dc.titleTwo genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer.
dc.typeJournal article
pubs.elements-id489119
pubs.organisational-groupCollege of Health
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