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000282365 1001_ $$aBouras, Emmanouil$$b0
000282365 245__ $$aGenome-wide interaction analysis of folate for colorectal cancer risk.
000282365 260__ $$aOxford$$bOxford University Press$$c2023
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000282365 500__ $$a2023 Nov;118(5):881-891
000282365 520__ $$aEpidemiological and experimental evidence suggests that higher folate intake is associated with a decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.We applied traditional case-control logistic regression, joint 3-degree of freedom (3DF), and a two-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC, in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO).Inverse associations of dietary, total folate, and folic acid supplement with CRC were found [odds ratio: 0.93 (95% confidence intervals [CI]: 0.90-0.96), and 0.91 (0.89-0.94) per quartile higher intake, and 0.82 (0.78-0.88) for users vs. non-users, respectively]. Interactions (P-interaction <5×10-8) of folic acid supplement and variants in the 3p25.2 locus [in the region of Synapsin II (SYN2)/tissue inhibitor of metalloproteinase 4 (TIMP4)] were found using the traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplement was associated with decreased CRC risk among those carrying the TT genotype (OR = 0.82; 95%CI: 0.79-0.86) but increased CRC risk among those carrying the TA genotype (OR = 1.63; 95%CI: 1.29-2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate.Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant -omics data are warranted to validate this finding.
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000282365 650_7 $$2Other$$aCRC
000282365 650_7 $$2Other$$aEuropean
000282365 650_7 $$2Other$$aGWIS
000282365 650_7 $$2Other$$aSYN2
000282365 650_7 $$2Other$$aTIMP4
000282365 650_7 $$2Other$$acolorectal cancer
000282365 650_7 $$2Other$$afolate
000282365 650_7 $$2Other$$afolic acid
000282365 650_7 $$2Other$$agenome-wide
000282365 650_7 $$2Other$$ainteraction
000282365 650_7 $$2Other$$asynapsin
000282365 650_7 $$2Other$$atissue inhibitor of metalloproteinase 4
000282365 7001_ $$aKim, Andre E$$b1
000282365 7001_ $$aLin, Yi$$b2
000282365 7001_ $$aMorrison, John$$b3
000282365 7001_ $$aDu, Mengmeng$$b4
000282365 7001_ $$aAlbanes, Demetrius$$b5
000282365 7001_ $$aBarry, Elizabeth L$$b6
000282365 7001_ $$aBaurley, James W$$b7
000282365 7001_ $$aBerndt, Sonja I$$b8
000282365 7001_ $$aBien, Stephanie A$$b9
000282365 7001_ $$aBishop, Timothy D$$b10
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000282365 7001_ $$aBudiarto, Arif$$b12
000282365 7001_ $$aBurnett-Hartman, Andrea$$b13
000282365 7001_ $$aCampbell, Peter T$$b14
000282365 7001_ $$aCarreras-Torres, Robert$$b15
000282365 7001_ $$aCasey, Graham$$b16
000282365 7001_ $$aCenggoro, Tjeng Wawan$$b17
000282365 7001_ $$aChan, Andrew T$$b18
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000282365 7001_ $$aConti, David V$$b20
000282365 7001_ $$aCotterchio, Michelle$$b21
000282365 7001_ $$aDevall, Matthew$$b22
000282365 7001_ $$aDiez-Obrero, Virginia$$b23
000282365 7001_ $$aDimou, Niki$$b24
000282365 7001_ $$aDrew, David A$$b25
000282365 7001_ $$aFigueiredo, Jane C$$b26
000282365 7001_ $$aGiles, Graham G$$b27
000282365 7001_ $$aGruber, Stephen B$$b28
000282365 7001_ $$aGunter, Marc J$$b29
000282365 7001_ $$aHarrison, Tabitha A$$b30
000282365 7001_ $$aHidaka, Akihisa$$b31
000282365 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b32$$udkfz
000282365 7001_ $$aHuyghe, Jeroen R$$b33
000282365 7001_ $$aJoshi, Amit D$$b34
000282365 7001_ $$aKawaguchi, Eric S$$b35
000282365 7001_ $$aKeku, Temitope O$$b36
000282365 7001_ $$aKundaje, Anshul$$b37
000282365 7001_ $$aLe Marchand, Loic$$b38
000282365 7001_ $$aLewinger, Juan Pablo$$b39
000282365 7001_ $$aLi, Li$$b40
000282365 7001_ $$aLynch, Brigid M$$b41
000282365 7001_ $$aMahesworo, Bharuno$$b42
000282365 7001_ $$aMännistö, Satu$$b43
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000282365 7001_ $$aPellatt, Andrew J$$b52
000282365 7001_ $$aPeoples, Anita R$$b53
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000282365 7001_ $$aPotter, John D$$b55
000282365 7001_ $$aQi, Lihong$$b56
000282365 7001_ $$aQu, Conghui$$b57
000282365 7001_ $$aRennert, Gad$$b58
000282365 7001_ $$aRuiz-Narvaez, Edward$$b59
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000282365 7001_ $$aStern, Mariana C$$b63
000282365 7001_ $$aSu, Yu-Ru$$b64
000282365 7001_ $$aTangen, Catherine M$$b65
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000282365 7001_ $$0P:(DE-He78)834e8bc4d74592e3b999100c157215f5$$aTian, Yu$$b67
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