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

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MARC

Bull, Caroline J. (author)

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

Article/chapterEnglish2020

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2020-12-17
BMC,2020
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:umu-178729
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-178729URI
https://doi.org/10.1186/s12916-020-01855-9DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-451937URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:145522654URI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Hälsovetenskap Näringslära hsv//swe
MEDICAL AND HEALTH SCIENCES Health Sciences Nutrition and Dietetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
Body mass index
Waist-to-hip ratio
Colorectal cancer
Mendelian randomization
Metabolism
NMR
Epidemiology
GECCO
CORECT
CCFR

Added entries (persons, corporate bodies, meetings, titles ...)

Bell, Joshua A. (author)
Murphy, Neil (author)
Sanderson, Eleanor (author)
Davey Smith, George (author)
Timpson, Nicholas J. (author)
Banbury, Barbara L. (author)
Albanes, Demetrius (author)
Berndt, Sonja I. (author)
Bezieau, Stephane (author)
Bishop, D. Timothy (author)
Brenner, Hermann (author)
Buchanan, Daniel D. (author)
Burnett-Hartman, Andrea (author)
Casey, Graham (author)
Castellvi-Bel, Sergi (author)
Chan, Andrew T. (author)
Chang-Claude, Jenny (author)
Cross, Amanda J. (author)
de la Chapelle, Albert (author)
Figueiredo, Jane C. (author)
Gallinger, Steven J. (author)
Gapstur, Susan M. (author)
Giles, Graham G. (author)
Gruber, Stephen B. (author)
Gsur, Andrea (author)
Hampe, Jochen (author)
Hampel, Heather (author)
Harrison, Tabitha A. (author)
Hoffmeister, Michael (author)
Hsu, Li (author)
Huang, Wen-Yi (author)
Huyghe, Jeroen R. (author)
Jenkins, Mark A. (author)
Joshu, Corinne E. (author)
Keku, Temitope O. (author)
Kuhn, Tilman (author)
Kweon, Sun-Seog (author)
Le Marchand, Loic (author)
Li, Christopher I. (author)
Li, Li (author)
Lindblom, AnnikaKarolinska Institutet (author)
Martin, Vicente (author)
May, Anne M. (author)
Milne, Roger L. (author)
Moreno, Victor (author)
Newcomb, Polly A. (author)
Offit, Kenneth (author)
Ogino, Shuji (author)
Phipps, Amanda I. (author)
Platz, Elizabeth A. (author)
Potter, John D. (author)
Qu, Conghui (author)
Quiros, J. Ramon (author)
Rennert, Gad (author)
Riboli, Elio (author)
Sakoda, Lori C. (author)
Schafmayer, Clemens (author)
Schoen, Robert E. (author)
Slattery, Martha L. (author)
Tangen, Catherine M. (author)
Tsilidis, Kostas K. (author)
Ulrich, Cornelia M. (author)
van Duijnhoven, Franzel J. B. (author)
van Guelpen, BethanyUmeå universitet,Onkologi,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)(Swepub:umu)beyvan99 (author)
Visvanathan, Kala (author)
Vodicka, Pavel (author)
Vodickova, Ludmila (author)
Wang, Hansong (author)
White, Emily (author)
Wolk, AlicjaKarolinska Institutet(Swepub:uu)alwol516 (author)
Woods, Michael O. (author)
Wu, Anna H. (author)
Campbell, Peter T. (author)
Zheng, Wei (author)
Peters, Ulrike (author)
Vincent, Emma E. (author)
Gunter, Marc J. (author)
Karolinska InstitutetOnkologi (creator_code:org_t)

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By the author/editor: Bull, Caroline J ...; Bell, Joshua A.; Murphy, Neil; Sanderson, Elean ...; Davey Smith, Geo ...; Timpson, Nichola ...; show more...; 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.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Health Sciences; and Nutrition and Di ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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