Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study

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Fältnamn	Indikatorer	Metadata
000		08046naa a2201465 4500
001		oai:DiVA.org:umu-178729
003		SwePub
008		210114s2020 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:DiVA.org:uu-451937
009		oai:prod.swepub.kib.ki.se:145522654
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1787292 URI
024	7	a https://doi.org/10.1186/s12916-020-01855-92 DOI
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4519372 URI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1455226542 URI
040		a (SwePub)umud (SwePub)uud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Bull, Caroline J.4 aut
245	1 0	a Adiposity, metabolites, and colorectal cancer risk :b Mendelian randomization study
264		c 2020-12-17
264	1	b BMC,c 2020
338		a electronic2 rdacarrier
520		a Background Higher 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. Methods 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. Results In sex-specific MR analyses, higher BMI (per 4.2 kg/m(2)) 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/m(2)) 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. Conclusions 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Hälsovetenskapx Näringslära0 (SwePub)303042 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Health Sciencesx Nutrition and Dietetics0 (SwePub)303042 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
653		a Body mass index
653		a Waist-to-hip ratio
653		a Colorectal cancer
653		a Mendelian randomization
653		a Metabolism
653		a NMR
653		a Epidemiology
653		a GECCO
653		a CORECT
653		a CCFR
700	1	a Bell, Joshua A.4 aut
700	1	a Murphy, Neil4 aut
700	1	a Sanderson, Eleanor4 aut
700	1	a Davey Smith, George4 aut
700	1	a Timpson, Nicholas J.4 aut
700	1	a Banbury, Barbara L.4 aut
700	1	a Albanes, Demetrius4 aut
700	1	a Berndt, Sonja I.4 aut
700	1	a Bezieau, Stephane4 aut
700	1	a Bishop, D. Timothy4 aut
700	1	a Brenner, Hermann4 aut
700	1	a Buchanan, Daniel D.4 aut
700	1	a Burnett-Hartman, Andrea4 aut
700	1	a Casey, Graham4 aut
700	1	a Castellvi-Bel, Sergi4 aut
700	1	a Chan, Andrew T.4 aut
700	1	a Chang-Claude, Jenny4 aut
700	1	a Cross, Amanda J.4 aut
700	1	a de la Chapelle, Albert4 aut
700	1	a Figueiredo, Jane C.4 aut
700	1	a Gallinger, Steven J.4 aut
700	1	a Gapstur, Susan M.4 aut
700	1	a Giles, Graham G.4 aut
700	1	a Gruber, Stephen B.4 aut
700	1	a Gsur, Andrea4 aut
700	1	a Hampe, Jochen4 aut
700	1	a Hampel, Heather4 aut
700	1	a Harrison, Tabitha A.4 aut
700	1	a Hoffmeister, Michael4 aut
700	1	a Hsu, Li4 aut
700	1	a Huang, Wen-Yi4 aut
700	1	a Huyghe, Jeroen R.4 aut
700	1	a Jenkins, Mark A.4 aut
700	1	a Joshu, Corinne E.4 aut
700	1	a Keku, Temitope O.4 aut
700	1	a Kuhn, Tilman4 aut
700	1	a Kweon, Sun-Seog4 aut
700	1	a Le Marchand, Loic4 aut
700	1	a Li, Christopher I.4 aut
700	1	a Li, Li4 aut
700	1	a Lindblom, Annikau Karolinska Institutet4 aut
700	1	a Martin, Vicente4 aut
700	1	a May, Anne M.4 aut
700	1	a Milne, Roger L.4 aut
700	1	a Moreno, Victor4 aut
700	1	a Newcomb, Polly A.4 aut
700	1	a Offit, Kenneth4 aut
700	1	a Ogino, Shuji4 aut
700	1	a Phipps, Amanda I.4 aut
700	1	a Platz, Elizabeth A.4 aut
700	1	a Potter, John D.4 aut
700	1	a Qu, Conghui4 aut
700	1	a Quiros, J. Ramon4 aut
700	1	a Rennert, Gad4 aut
700	1	a Riboli, Elio4 aut
700	1	a Sakoda, Lori C.4 aut
700	1	a Schafmayer, Clemens4 aut
700	1	a Schoen, Robert E.4 aut
700	1	a Slattery, Martha L.4 aut
700	1	a Tangen, Catherine M.4 aut
700	1	a Tsilidis, Kostas K.4 aut
700	1	a Ulrich, Cornelia M.4 aut
700	1	a van Duijnhoven, Franzel J. B.4 aut
700	1	a van Guelpen, Bethanyu Umeå universitet,Onkologi,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)4 aut0 (Swepub:umu)beyvan99
700	1	a Visvanathan, Kala4 aut
700	1	a Vodicka, Pavel4 aut
700	1	a Vodickova, Ludmila4 aut
700	1	a Wang, Hansong4 aut
700	1	a White, Emily4 aut
700	1	a Wolk, Alicjau Karolinska Institutet4 aut0 (Swepub:uu)alwol516
700	1	a Woods, Michael O.4 aut
700	1	a Wu, Anna H.4 aut
700	1	a Campbell, Peter T.4 aut
700	1	a Zheng, Wei4 aut
700	1	a Peters, Ulrike4 aut
700	1	a Vincent, Emma E.4 aut
700	1	a Gunter, Marc J.4 aut
710	2	a Karolinska Institutetb Onkologi4 org
773	0	t BMC Medicined : BMCg 18:1q 18:1x 1741-7015
856	4	u https://umu.diva-portal.org/smash/get/diva2:1517677/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4	u https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01855-9
856	4	u https://doi.org/10.1186/s12916-020-01855-9y Fulltext
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-178729
856	4 8	u https://doi.org/10.1186/s12916-020-01855-9
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-451937
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:145522654

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Av författaren/redakt...: Bull, Caroline J ...; Bell, Joshua A.; Murphy, Neil; Sanderson, Elean ...; Davey Smith, Geo ...; Timpson, Nichola ...; visa fler...; Banbury, Barbara ...; Albanes, Demetri ...; Berndt, Sonja I.; Bezieau, Stephan ...; Bishop, D. Timot ...; Brenner, Hermann; Buchanan, Daniel ...; Burnett-Hartman, ...; Casey, Graham; Castellvi-Bel, S ...; Chan, Andrew T.; Chang-Claude, Je ...; Cross, Amanda J.; de la Chapelle, ...; Figueiredo, Jane ...; Gallinger, Steve ...; Gapstur, Susan M ...; Giles, Graham G.; Gruber, Stephen ...; Gsur, Andrea; Hampe, Jochen; Hampel, Heather; Harrison, Tabith ...; Hoffmeister, Mic ...; Hsu, Li; Huang, Wen-Yi; Huyghe, Jeroen R ...; Jenkins, Mark A.; Joshu, Corinne E ...; Keku, Temitope O ...; Kuhn, Tilman; Kweon, Sun-Seog; Le Marchand, Loi ...; Li, Christopher ...; Li, Li; Lindblom, Annika; Martin, Vicente; May, Anne M.; Milne, Roger L.; Moreno, Victor; Newcomb, Polly A ...; Offit, Kenneth; Ogino, Shuji; Phipps, Amanda I ...; Platz, Elizabeth ...; Potter, John D.; Qu, Conghui; Quiros, J. Ramon; Rennert, Gad; Riboli, Elio; Sakoda, Lori C.; Schafmayer, Clem ...; Schoen, Robert E ...; Slattery, Martha ...; Tangen, Catherin ...; Tsilidis, Kostas ...; Ulrich, Cornelia ...; van Duijnhoven, ...; van Guelpen, Bet ...; Visvanathan, Kal ...; Vodicka, Pavel; Vodickova, Ludmi ...; Wang, Hansong; White, Emily; Wolk, Alicja; Woods, Michael O ...; Wu, Anna H.; Campbell, Peter ...; Zheng, Wei; Peters, Ulrike; Vincent, Emma E.; Gunter, Marc J.; visa färre...

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