000166519 001__ 166519
000166519 005__ 20240229123230.0
000166519 0247_ $$2doi$$a10.1186/s12916-020-01855-9
000166519 0247_ $$2pmid$$apmid:33327948
000166519 0247_ $$2pmc$$apmc:PMC7745469
000166519 0247_ $$2altmetric$$aaltmetric:96139643
000166519 037__ $$aDKFZ-2020-02962
000166519 041__ $$aeng
000166519 082__ $$a610
000166519 1001_ $$00000-0002-2176-5120$$aBull, Caroline J$$b0
000166519 245__ $$aAdiposity, metabolites, and colorectal cancer risk: Mendelian randomization study.
000166519 260__ $$aHeidelberg [u.a.]$$bSpringer$$c2020
000166519 3367_ $$2DRIVER$$aarticle
000166519 3367_ $$2DataCite$$aOutput Types/Journal article
000166519 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1611320731_15622
000166519 3367_ $$2BibTeX$$aARTICLE
000166519 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000166519 3367_ $$00$$2EndNote$$aJournal Article
000166519 500__ $$a2020 Dec 17;18(1):396
000166519 520__ $$aHigher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood.We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models.In sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles.Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.
000166519 536__ $$0G:(DE-HGF)POF3-313$$a313 - Cancer risk factors and prevention (POF3-313)$$cPOF3-313$$fPOF III$$x0
000166519 588__ $$aDataset connected to CrossRef, PubMed,
000166519 650_7 $$2Other$$aBody mass index
000166519 650_7 $$2Other$$aCCFR
000166519 650_7 $$2Other$$aCORECT
000166519 650_7 $$2Other$$aColorectal cancer
000166519 650_7 $$2Other$$aEpidemiology
000166519 650_7 $$2Other$$aGECCO
000166519 650_7 $$2Other$$aMendelian randomization
000166519 650_7 $$2Other$$aMetabolism
000166519 650_7 $$2Other$$aNMR
000166519 650_7 $$2Other$$aWaist-to-hip ratio
000166519 7001_ $$aBell, Joshua A$$b1
000166519 7001_ $$aMurphy, Neil$$b2
000166519 7001_ $$aSanderson, Eleanor$$b3
000166519 7001_ $$aDavey Smith, George$$b4
000166519 7001_ $$aTimpson, Nicholas J$$b5
000166519 7001_ $$aBanbury, Barbara L$$b6
000166519 7001_ $$aAlbanes, Demetrius$$b7
000166519 7001_ $$aBerndt, Sonja I$$b8
000166519 7001_ $$aBézieau, Stéphane$$b9
000166519 7001_ $$aBishop, D Timothy$$b10
000166519 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b11$$udkfz
000166519 7001_ $$aBuchanan, Daniel D$$b12
000166519 7001_ $$aBurnett-Hartman, Andrea$$b13
000166519 7001_ $$aCasey, Graham$$b14
000166519 7001_ $$aCastellví-Bel, Sergi$$b15
000166519 7001_ $$aChan, Andrew T$$b16
000166519 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b17$$udkfz
000166519 7001_ $$aCross, Amanda J$$b18
000166519 7001_ $$ade la Chapelle, Albert$$b19
000166519 7001_ $$aFigueiredo, Jane C$$b20
000166519 7001_ $$aGallinger, Steven J$$b21
000166519 7001_ $$aGapstur, Susan M$$b22
000166519 7001_ $$aGiles, Graham G$$b23
000166519 7001_ $$aGruber, Stephen B$$b24
000166519 7001_ $$aGsur, Andrea$$b25
000166519 7001_ $$aHampe, Jochen$$b26
000166519 7001_ $$aHampel, Heather$$b27
000166519 7001_ $$aHarrison, Tabitha A$$b28
000166519 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b29$$udkfz
000166519 7001_ $$aHsu, Li$$b30
000166519 7001_ $$aHuang, Wen-Yi$$b31
000166519 7001_ $$aHuyghe, Jeroen R$$b32
000166519 7001_ $$aJenkins, Mark A$$b33
000166519 7001_ $$aJoshu, Corinne E$$b34
000166519 7001_ $$aKeku, Temitope O$$b35
000166519 7001_ $$0P:(DE-He78)0907a10ba1dc8f53f04907f54f6fdcfe$$aKühn, Tilman$$b36$$udkfz
000166519 7001_ $$aKweon, Sun-Seog$$b37
000166519 7001_ $$aLe Marchand, Loic$$b38
000166519 7001_ $$aLi, Christopher I$$b39
000166519 7001_ $$aLi, Li$$b40
000166519 7001_ $$aLindblom, Annika$$b41
000166519 7001_ $$aMartín, Vicente$$b42
000166519 7001_ $$aMay, Anne M$$b43
000166519 7001_ $$aMilne, Roger L$$b44
000166519 7001_ $$aMoreno, Victor$$b45
000166519 7001_ $$aNewcomb, Polly A$$b46
000166519 7001_ $$aOffit, Kenneth$$b47
000166519 7001_ $$aOgino, Shuji$$b48
000166519 7001_ $$aPhipps, Amanda I$$b49
000166519 7001_ $$aPlatz, Elizabeth A$$b50
000166519 7001_ $$aPotter, John D$$b51
000166519 7001_ $$aQu, Conghui$$b52
000166519 7001_ $$aQuirós, J Ramón$$b53
000166519 7001_ $$aRennert, Gad$$b54
000166519 7001_ $$aRiboli, Elio$$b55
000166519 7001_ $$aSakoda, Lori C$$b56
000166519 7001_ $$aSchafmayer, Clemens$$b57
000166519 7001_ $$aSchoen, Robert E$$b58
000166519 7001_ $$aSlattery, Martha L$$b59
000166519 7001_ $$aTangen, Catherine M$$b60
000166519 7001_ $$aTsilidis, Kostas K$$b61
000166519 7001_ $$aUlrich, Cornelia M$$b62
000166519 7001_ $$avan Duijnhoven, Fränzel J B$$b63
000166519 7001_ $$avan Guelpen, Bethany$$b64
000166519 7001_ $$aVisvanathan, Kala$$b65
000166519 7001_ $$aVodicka, Pavel$$b66
000166519 7001_ $$aVodickova, Ludmila$$b67
000166519 7001_ $$aWang, Hansong$$b68
000166519 7001_ $$aWhite, Emily$$b69
000166519 7001_ $$aWolk, Alicja$$b70
000166519 7001_ $$aWoods, Michael O$$b71
000166519 7001_ $$aWu, Anna H$$b72
000166519 7001_ $$aCampbell, Peter T$$b73
000166519 7001_ $$aZheng, Wei$$b74
000166519 7001_ $$aPeters, Ulrike$$b75
000166519 7001_ $$aVincent, Emma E$$b76
000166519 7001_ $$aGunter, Marc J$$b77
000166519 773__ $$0PERI:(DE-600)2131669-7$$a10.1186/s12916-020-01855-9$$gVol. 18, no. 1, p. 396$$n1$$p396$$tBMC medicine$$v18$$x1741-7015$$y2020
000166519 909CO $$ooai:inrepo02.dkfz.de:166519$$pVDB
000166519 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ
000166519 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aDeutsches Krebsforschungszentrum$$b17$$kDKFZ
000166519 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aDeutsches Krebsforschungszentrum$$b29$$kDKFZ
000166519 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)0907a10ba1dc8f53f04907f54f6fdcfe$$aDeutsches Krebsforschungszentrum$$b36$$kDKFZ
000166519 9131_ $$0G:(DE-HGF)POF3-313$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vCancer risk factors and prevention$$x0
000166519 9141_ $$y2020
000166519 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBMC MED : 2018$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Open peer review$$d2020-09-05
000166519 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bBMC MED : 2018$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2020-09-05
000166519 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2020-09-05
000166519 9201_ $$0I:(DE-He78)C070-20160331$$kC070$$lC070 Klinische Epidemiologie und Alternf.$$x0
000166519 9201_ $$0I:(DE-He78)C120-20160331$$kC120$$lPräventive Onkologie$$x1
000166519 9201_ $$0I:(DE-He78)HD01-20160331$$kHD01$$lDKTK HD zentral$$x2
000166519 9201_ $$0I:(DE-He78)C020-20160331$$kC020$$lC020 Epidemiologie von Krebs$$x3
000166519 980__ $$ajournal
000166519 980__ $$aVDB
000166519 980__ $$aI:(DE-He78)C070-20160331
000166519 980__ $$aI:(DE-He78)C120-20160331
000166519 980__ $$aI:(DE-He78)HD01-20160331
000166519 980__ $$aI:(DE-He78)C020-20160331
000166519 980__ $$aUNRESTRICTED