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000157054 1001_ $$aWang, Xiaoliang$$b0
000157054 245__ $$aExploratory genome-wide interaction analysis of non-steroidal anti-inflammatory drugs and predicted gene expression on colorectal cancer risk.
000157054 260__ $$aPhiladelphia, Pa.$$bAACR$$c2020
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000157054 500__ $$a2020 Sep;29(9):1800-1808
000157054 520__ $$aRegular use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer (CRC). Genome-wide interaction analysis on single variants (G×E) has identified several SNPs that may interact with NSAIDs to confer CRC risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to CRC risk.Genetically predicted gene expressions were tested for interaction with NSAID use on CRC risk among 19,258 CRC cases and 18,597 controls from 21 observational studies. A Mixed Score Test for Interactions (MiSTi) approach was used to jointly assess G×E effects which are modeled via fixed interaction effects of the weighted burden within each gene sets (burden) and residual G×E effects (variance). A false discovery rate (FDR) at 0.2 was applied to correct for multiple testing.Among the 4,840 genes tested, genetically predicted expression levels of four genes modified the effect of any NSAID use on CRC risk, including DPP10 (P-G×E=1.96×10-4), KRT16 (P-G×E=2.3×10-4), CD14 (P-G×E=9.38×10-4), and CYP27A1 (P-G×E=1.44×10-3). There was a significant interaction between expression level of RP11-89N17 and regular use of aspirin only on CRC risk (P-G×E=3.23×10-5). No interactions were observed between predicted gene expression and non-aspirin NSAID use at FDR<0.2.By incorporating functional information, we discovered several novel genes that interacted with NSAID use.These findings provide preliminary support that could help understand the chemopreventive mechanisms of NSAIDs on CRC.
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000157054 7001_ $$aSu, Yu-Ru$$b1
000157054 7001_ $$aPetersen, Paneen S$$b2
000157054 7001_ $$aBien, Stephanie$$b3
000157054 7001_ $$aSchmit, Stephanie L$$b4
000157054 7001_ $$00000-0002-8813-0816$$aDrew, David A$$b5
000157054 7001_ $$aAlbanes, Demetrius$$b6
000157054 7001_ $$aBerndt, Sonja I$$b7
000157054 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b8$$udkfz
000157054 7001_ $$aCampbell, Peter T$$b9
000157054 7001_ $$aCasey, Graham$$b10
000157054 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b11$$udkfz
000157054 7001_ $$aGallinger, Steven$$b12
000157054 7001_ $$00000-0001-8656-7822$$aGruber, Stephen B$$b13
000157054 7001_ $$00000-0001-6902-1836$$aHaile, Robert W$$b14
000157054 7001_ $$00000-0002-4173-7530$$aHarrison, Tabitha A$$b15
000157054 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b16$$udkfz
000157054 7001_ $$aJacobs, Eric J$$b17
000157054 7001_ $$aJenkins, Mark A$$b18
000157054 7001_ $$aJoshi, Amit D$$b19
000157054 7001_ $$aLi, Li$$b20
000157054 7001_ $$aLin, Yi$$b21
000157054 7001_ $$aLindor, Noralane M$$b22
000157054 7001_ $$aLe Marchand, Loic$$b23
000157054 7001_ $$00000-0003-0552-2804$$aMartín, Vicente$$b24
000157054 7001_ $$00000-0001-5764-7268$$aMilne, Roger L$$b25
000157054 7001_ $$00000-0002-1627-5047$$aMaclnnis, Robert$$b26
000157054 7001_ $$00000-0002-2818-5487$$aMoreno, Victor$$b27
000157054 7001_ $$aNan, Hongmei$$b28
000157054 7001_ $$aNewcomb, Polly A$$b29
000157054 7001_ $$00000-0001-5439-1500$$aPotter, John D$$b30
000157054 7001_ $$aRennert, Gad$$b31
000157054 7001_ $$00000-0001-5772-2977$$aRennert, Hedy S$$b32
000157054 7001_ $$00000-0002-1655-6543$$aSlattery, Martha L$$b33
000157054 7001_ $$aThibodeau, Stephen N$$b34
000157054 7001_ $$00000-0002-3834-1535$$aWeinstein, Stephanie J$$b35
000157054 7001_ $$aWoods, Michael O$$b36
000157054 7001_ $$aChan, Andrew T$$b37
000157054 7001_ $$aWhite, Emily$$b38
000157054 7001_ $$aHsu, Li$$b39
000157054 7001_ $$aPeters, Ulrike$$b40
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