دورية أكاديمية
Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study
| العنوان: | Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study |
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| المؤلفون: | Bull, CJ, Bell, JA, Murphy, N, Sanderson, E, Davey Smith, G, Timpson, NJ, Banbury, BL, Albanes, D, Berndt, SI, Bezieau, S, Bishop, DT, Brenner, H, Buchanan, DD, Burnett-Hartman, A, Casey, G, Castellvi-Bel, S, Chan, AT, Chang-Claude, J, Cross, AJ, De la Chapelle, A, Figueiredo, JC, Gallinger, SJ, Gapstur, SM, Giles, GG, Gruber, SB, Gsur, A, Hampe, J, Hampel, H, Harrison, TA, Hoffmeister, M, Hsu, L, Huang, W-Y, Huyghe, JR, Jenkins, MA, Joshu, CE, Keku, TO, Kuhn, T, Kweon, S-S, Le Marchand, L, Li, CI, Li, L, Lindblom, A, Martin, V, May, AM, Milne, RL, Moreno, V, Newcomb, PA, Offit, K, Ogino, S, Phipps, AI, Platz, EA, Potter, JD, Qu, C, Quiros, JR, Rennert, G, Riboli, E, Sakoda, LC, Schafmayer, C, Schoen, RE, Slattery, ML, Tangen, CM, Tsilidis, KK, Ulrich, CM, Van Duijnhoven, FJB, Van Guelpen, B, Visvanathan, K, Vodicka, P, Vodickova, L, Wang, H, White, E, Wolk, A, Woods, MO, Wu, AH, Campbell, PT, Zheng, W, Peters, U, Vincent, EE, Gunter, MJ |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2020 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, Body mass index, Waist-to-hip ratio, Colorectal cancer, Mendelian randomization, Metabolism, NMR, Epidemiology, GECCO, CORECT, CCFR, BODY-MASS INDEX, INSULIN-RESISTANCE, GENOME-WIDE, METAANALYSIS, DISTAL, BIAS, FAT, INSTRUMENTS, ASSOCIATION, PROTEINS |
| الوصف: | 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/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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1741-7015 |
| العلاقة: | BMC Medicine; http://hdl.handle.net/10044/1/85629Test |
| DOI: | 10.1186/s12916-020-01855-9 |
| الإتاحة: | https://doi.org/10.1186/s12916-020-01855-9Test http://hdl.handle.net/10044/1/85629Test |
| حقوق: | © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0Test/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0Test/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.51595B11 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17417015 |
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| DOI: | 10.1186/s12916-020-01855-9 |