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

. 2020 Dec 17 ; 18 (1) : 396. [epub] 20201217

Jazyk angličtina Země Velká Británie, Anglie Médium electronic

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid33327948

Grantová podpora
R01 CA137178 NCI NIH HHS - United States
19169 Cancer Research UK - United Kingdom
P30 DK058404 NIDDK NIH HHS - United States
R01 CA189184 NCI NIH HHS - United States
K05 CA154337 NCI NIH HHS - United States
HHSN268201600018C NHLBI NIH HHS - United States
P01 CA087969 NCI NIH HHS - United States
R21 CA191312 NCI NIH HHS - United States
Wellcome Trust - United Kingdom
MR/M012190/1 Medical Research Council - United Kingdom
HHSN268201600001C NHLBI NIH HHS - United States
P30 CA006973 NCI NIH HHS - United States
HHSN268201600003C NHLBI NIH HHS - United States
MC_UU_00011/2 Medical Research Council - United Kingdom
R01 CA059045 NCI NIH HHS - United States
K07 CA190673 NCI NIH HHS - United States
U01 CA182883 NCI NIH HHS - United States
U10 CA037429 NCI NIH HHS - United States
R01 CA114347 NCI NIH HHS - United States
MC_UU_12013/3 Medical Research Council - United Kingdom
P30 CA015704 NCI NIH HHS - United States
U01 CA137088 NCI NIH HHS - United States
R01 CA076366 NCI NIH HHS - United States
P30 CA047904 NCI NIH HHS - United States
U19 CA148107 NCI NIH HHS - United States
T32 ES013678 NIEHS NIH HHS - United States
UG1 CA189974 NCI NIH HHS - United States
R01 CA151993 NCI NIH HHS - United States
R37 CA054281 NCI NIH HHS - United States
P50 CA127003 NCI NIH HHS - United States
U01 CA206110 NCI NIH HHS - United States
R01 CA048998 NCI NIH HHS - United States
19167 Cancer Research UK - United Kingdom
U01 CA167551 NCI NIH HHS - United States
P30 CA008748 NCI NIH HHS - United States
HHSN261201500005C NCI NIH HHS - United States
R35 CA197735 NCI NIH HHS - United States
202802/Z/16/Z Wellcome Trust - United Kingdom
HHSN268201600004C NHLBI NIH HHS - United States
U01 CA122839 NCI NIH HHS - United States
UM1 CA167552 NCI NIH HHS - United States
C18281/A19169 Cancer Research UK - United Kingdom
U01 HG004438 NHGRI NIH HHS - United States
17/0005587 Diabetes UK - United Kingdom
R01 CA207371 NCI NIH HHS - United States
U01 HG004446 NHGRI NIH HHS - United States
R01 CA042182 NCI NIH HHS - United States
U01 CA074794 NCI NIH HHS - United States
UM1 CA186107 NCI NIH HHS - United States
U01 CA164930 NCI NIH HHS - United States
P01 CA055075 NCI NIH HHS - United States
25004 Cancer Research UK - United Kingdom
R03 CA153323 NCI NIH HHS - United States
R01 CA097325 NCI NIH HHS - United States
10589 Cancer Research UK - United Kingdom
HHSN268201200008I NHLBI NIH HHS - United States
K05 CA152715 NCI NIH HHS - United States
001 World Health Organization - International
Z01 CP010200 NCI NIH HHS - United States
29019 Cancer Research UK - United Kingdom
KL2 TR000421 NCATS NIH HHS - United States
204813/Z/16/Z Wellcome Trust - United Kingdom
MC_UU_00011/1 Medical Research Council - United Kingdom
R01 CA063464 NCI NIH HHS - United States
R01 CA081488 NCI NIH HHS - United States
P01 CA033619 NCI NIH HHS - United States
U01 CA074783 NCI NIH HHS - United States

Odkazy

PubMed 33327948
PubMed Central PMC7745469
DOI 10.1186/s12916-020-01855-9
PII: 10.1186/s12916-020-01855-9
Knihovny.cz E-zdroje

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 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.

Behavioral and Epidemiology Research Group American Cancer Society Atlanta GA USA

Biomedicine Institute University of León León Spain

Broad Institute of Harvard and MIT Cambridge MA USA

Broad Institute of MIT and Harvard Cambridge MA USA

Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia

Cancer Immunology and Cancer Epidemiology Programs Dana Farber Harvard Cancer Center Boston MA USA

Center for Gastrointestinal Biology and Disease University of North Carolina Chapel Hill NC USA

Center for Public Health Genomics University of Virginia Charlottesville VA USA

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne Victoria Australia

Centre for Public Health Research Massey University Wellington New Zealand

Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA USA

CIBER Epidemiología y Salud Pública Madrid Spain

Clalit National Cancer Control Center Haifa Israel

Clinical and Translational Epidemiology Unit Massachusetts General Hospital and Harvard Medical School Boston MA USA

Clinical Genetics Service Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA

Colorectal Oncogenomics Group Department of Clinical Pathology The University of Melbourne Parkville Victoria Australia

Department of Biostatistics University of Washington Seattle WA USA

Department of Cancer Biology and Genetics and the Comprehensive Cancer Center The Ohio State University Columbus OH USA

Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden

Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain

Department of Community Medicine and Epidemiology Lady Davis Carmel Medical Center Haifa Israel

Department of Epidemiology and Biostatistics Imperial College London Norfolk Place London UK

Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK

Department of Epidemiology Harvard T H Chan School of Public Health Boston MA USA

Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Department of Epidemiology University of Washington School of Public Health Seattle WA USA

Department of Epidemiology University of Washington Seattle WA USA

Department of Family Medicine University of Virginia Charlottesville VA USA

Department of General Surgery University Hospital Rostock Rostock Germany

Department of Hygiene and Epidemiology University of Ioannina School of Medicine Ioannina Greece

Department of Internal Medicine University of Utah Salt Lake City UT USA

Department of Medicine 1 University Hospital Dresden Technische Universität Dresden Dresden Germany

Department of Medicine and Epidemiology University of Pittsburgh Medical Center Pittsburgh PA USA

Department of Medicine Samuel Oschin Comprehensive Cancer Institute Cedars Sinai Medical Center Los Angeles CA USA

Department of Medicine Weill Cornell Medical College New York NY USA

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden

Department of Preventive Medicine and USC Norris Comprehensive Cancer Center Keck School of Medicine University of Southern California Los Angeles CA USA

Department of Preventive Medicine Chonnam National University Medical School Gwangju South Korea

Department of Preventive Medicine Keck School of Medicine University of Southern California Los Angeles CA USA

Department of Radiation Sciences Oncology Unit Umeå University Umeå Sweden

Discipline of Genetics Memorial University of Newfoundland St John's Canada

Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda MD USA

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany

Division of Epidemiology Department of Medicine Vanderbilt Ingram Cancer Center Vanderbilt Epidemiology Center Vanderbilt University School of Medicine Nashville TN USA

Division of Gastroenterology Massachusetts General Hospital and Harvard Medical School Boston MA USA

Division of Human Genetics Department of Internal Medicine The Ohio State University Comprehensive Cancer Center Columbus OH USA

Division of Human Nutrition and Health Wageningen University and Research Wageningen The Netherlands

Division of Preventive Oncology German Cancer Research Center Heidelberg Germany

Division of Research Kaiser Permanente Northern California Oakland CA USA

Epidemiology Research Program American Cancer Society Atlanta GA USA

Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic

Gastroenterology Department Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer University of Barcelona Barcelona Spain

Genomic Medicine and Family Cancer Clinic The Royal Melbourne Hospital Parkville Victoria Australia

German Cancer Consortium Heidelberg Germany

Health Sciences Centre University of Canterbury Christchurch New Zealand

Huntsman Cancer Institute and Department of Population Health Sciences University of Utah Salt Lake City UT USA

Institute for Health Research Kaiser Permanente Colorado Denver CO USA

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Cancer Research Department of Medicine 1 Medical University Vienna Vienna Austria

Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

Jeonnam Regional Cancer Center Chonnam National University Hwasun Hospital Hwasun South Korea

Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht University Utrecht The Netherlands

Leeds Institute of Cancer and Pathology University of Leeds Leeds UK

Lunenfeld Tanenbaum Research Institute Mount Sinai Hospital University of Toronto Toronto Ontario Canada

MRC Integrative Epidemiology Unit at the University of Bristol Oakfield House Bristol UK

Nutrition and Metabolism Section International Agency for Research on Cancer World Health Organization Lyon France

ONCOBEL Program Bellvitge Biomedical Research Institute L'Hospitalet de Llobregat Barcelona Spain

Oncology Data Analytics Program Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Population Health Sciences Bristol Medical School University of Bristol Bristol UK

Precision Medicine School of Clinical Sciences at Monash Health Monash University Clayton Victoria Australia

Program in MPE Molecular Pathological Epidemiology Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston MA USA

Public Health Directorate Asturias Spain

Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA

Ruth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa Israel

School of Cellular and Molecular Medicine University of Bristol Bristol UK

School of Public Health University of Washington Seattle WA USA

Service de Génétique Médicale Centre Hospitalier Universitaire Nantes Nantes France

SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle WA USA

University Cancer Centre Hamburg University Medical Centre Hamburg Eppendorf Hamburg Germany

University of Hawaii Cancer Center Honolulu HI USA

University of Southern California Preventative Medicine CA Los Angeles USA

University of Washington Seattle WA USA

Victorian Comprehensive Cancer Centre University of Melbourne Centre for Cancer Research Parkville Victoria Australia

Wallenberg Centre for Molecular Medicine Umeå University Umeå Sweden

Zobrazit více v PubMed

Sung H, Siegel RL, Rosenberg PS, Jemal A. Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registry. Lancet Public Health. 2019;4(3):E137-E147. 10.1016/S2468-2667(18)30267-6. PubMed

Mauri G, Sartore-Bianchi A, Russo AG, Marsoni S, Bardelli A, Siena S. Early-onset colorectal cancer in young individuals. Mol Oncol. 2019;13(2):109–131. doi: 10.1002/1878-0261.12417. PubMed DOI PMC

World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Expert Report. Diet, nutrition, physical activity and colorectal cancer. 2018.

Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. Body fatness and cancer—viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794–798. doi: 10.1056/NEJMsr1606602. PubMed DOI PMC

Luo J, Hendryx M, Manson JE, Figueiredo JC, LeBlanc ES, Barrington W, et al. Intentional weight loss and obesity-related cancer risk. JNCI Cancer Spectrum. 2019;3(4):pkz054. doi: 10.1093/jncics/pkz054. PubMed DOI PMC

Davey Smith G, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32(1):1–22. doi: 10.1093/ije/dyg070. PubMed DOI

Thrift AP, Gong J, Peters U, Chang-Claude J, Rudolph A, Slattery ML, et al. Mendelian randomization study of body mass index and colorectal cancer risk. Cancer Epidemiol Biomark Prev. 2015;24(7):1024–1031. doi: 10.1158/1055-9965.EPI-14-1309. PubMed DOI PMC

Jarvis D, Mitchell JS, Law PJ, Palin K, Tuupanen S, Gylfe A, et al. Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer. Br J Cancer. 2016;115(2):266–272. doi: 10.1038/bjc.2016.188. PubMed DOI PMC

Gao C, Patel CJ, Michailidou K, Peters U, Gong J, Schildkraut J, et al. Mendelian randomization study of adiposity-related traits and risk of breast, ovarian, prostate, lung and colorectal cancer. Int J Epidemiol. 2016;45(3):896–908. doi: 10.1093/ije/dyw129. PubMed DOI PMC

Gunter MJ, Riboli E. Obesity and gastrointestinal cancers—where do we go from here? Nature Rev Gastroenterol Hepatol. 2018;15(11):651. doi: 10.1038/s41575-018-0073-y. PubMed DOI

Dombrowski SU, Knittle K, Avenell A, Araujo-Soares V, Sniehotta FF. Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials. BMJ. 2014;348:g2646. doi: 10.1136/bmj.g2646. PubMed DOI PMC

World Cancer Research Fund/American Institute for Cancer Research. Diet, nutrition, physical activity and colorectal cancer: continuous update project. 2017.

Lawlor DA. Commentary: two-sample Mendelian randomization: opportunities and challenges. Int J Epidemiol. 2016;45(3):908. doi: 10.1093/ije/dyw127. PubMed DOI PMC

Aschard H, Vilhjálmsson BJ, Joshi AD, Price AL, Kraft P. Adjusting for heritable covariates can bias effect estimates in genome-wide association studies. Am J Hum Genet. 2015;96(2):329–339. doi: 10.1016/j.ajhg.2014.12.021. PubMed DOI PMC

Holmes MV, Ala-Korpela M, Davey SG. Mendelian randomization in cardiometabolic disease: challenges in evaluating causality. Nat Rev Cardiol. 2017;14:577–590. doi: 10.1038/nrcardio.2017.78. PubMed DOI PMC

Hartwig FP, Tilling K, Davey-Smith G, Lawlor DA, Borges M-CJB. Bias in two-sample Mendelian randomization by using covariable-adjusted summary associations. bioRxiv. 2019. p. 816363. PubMed PMC

Holmes MV, Davey SG. Problems in interpreting and using GWAS of conditional phenotypes illustrated by ‘alcohol GWAS’. Mol Psych. 2019;24(2):167. doi: 10.1038/s41380-018-0037-1. PubMed DOI PMC

Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014;156(1):20–44. doi: 10.1016/j.cell.2013.12.012. PubMed DOI PMC

Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840–846. doi: 10.1038/nature05482. PubMed DOI

Würtz P, Wang Q, Kangas AJ, Richmond RC, Skarp J, Tiainen M, et al. Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change. PLoS Med. 2014;11(12):e1001765. doi: 10.1371/journal.pmed.1001765. PubMed DOI PMC

Rodriguez-Broadbent H, Law PJ, Sud A, Palin K, Tuupanen S, Gylfe A, et al. Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer. Int J Cancer. 2017;140(12):2701–2708. doi: 10.1002/ijc.30709. PubMed DOI PMC

Song M, Lu Y, Gunter M, Murphy N, Banbury BL, Ma W, et al. Type 2 diabetes and glycemic traits in relation to colorectal cancer risk: a Mendelian randomization study. 2018.

May-Wilson S, Sud A, Law PJ, Palin K, Tuupanen S, Gylfe A, et al. Pro-inflammatory fatty acid profile and colorectal cancer risk: a Mendelian randomisation analysis. Eur J Cancer. 2017;84:228–238. doi: 10.1016/j.ejca.2017.07.034. PubMed DOI PMC

Würtz P, Kangas AJ, Soininen P, Lawlor DA, Davey Smith G, Ala-Korpela M. Quantitative serum NMR metabolomics in large-scale epidemiology: a primer on-omic technology. Am J Epidemiol. 2017:kwx016. PubMed PMC

Kettunen J, Demirkan A, Würtz P, Draisma HH, Haller T, Rawal R, et al. Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. Nat Commun. 2016;7:11122. doi: 10.1038/ncomms11122. PubMed DOI PMC

Huyghe JR, Bien SA, Harrison TA, Kang HM, Chen S, Schmit SL, et al. Discovery of common and rare genetic risk variants for colorectal cancer. Nature Genet. 2019;51(1):76. doi: 10.1038/s41588-018-0286-6. PubMed DOI PMC

Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Gen. 2014;23(R1):R89–R98. doi: 10.1093/hmg/ddu328. PubMed DOI PMC

Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304–314. doi: 10.1002/gepi.21965. PubMed DOI PMC

Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46(6):1985–1998. doi: 10.1093/ije/dyx102. PubMed DOI PMC

Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–525. doi: 10.1093/ije/dyv080. PubMed DOI PMC

Sterne JA, Davey SG. Sifting the evidence—what’s wrong with significance tests? BMJ. 2001;322(7280):226–231. doi: 10.1136/bmj.322.7280.226. PubMed DOI PMC

Wasserstein RL, Lazar NA. The ASA’s statement on p-values: context, process, and purpose. Am Statistician. 2016;70(2):129–133. doi: 10.1080/00031305.2016.1154108. DOI

Pulit SL, Stoneman C, Morris AP, Wood AR, Glastonbury CA, Tyrrell J, et al. Metaanalysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry. Hum Mol Gen. 2019;28(1):166–74. PubMed PMC

Shim H, Chasman DI, Smith JD, Mora S, Ridker PM, Nickerson DA, et al. A multivariate genome-wide association analysis of 10 LDL subfractions, and their response to statin treatment, in 1868 Caucasians. PLoS One. 2015;10(4):e0120758. doi: 10.1371/journal.pone.0120758. PubMed DOI PMC

Haycock PC, Burgess S, Wade KH, Bowden J, Relton C, Davey SG. Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies. Am J Clin Nutr. 2016;103(4):965–978. doi: 10.3945/ajcn.115.118216. PubMed DOI PMC

Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-base platform supports systematic causal inference across the human phenome. eLife. 2018;7:e34408. doi: 10.7554/eLife.34408. PubMed DOI PMC

Burgess S, Bowden J, Fall T, Ingelsson E, Thompson SG. Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants. Epidemiology. 2017;28(1):30. doi: 10.1097/EDE.0000000000000559. PubMed DOI PMC

Wald A. The fitting of straight lines if both variables are subject to error. Ann Mathematical Statistics. 1940;11(3):284–300. doi: 10.1214/aoms/1177731868. DOI

Bowden J, Hemani G, Davey Smith GJAjoe. Invited commentary: Detecting individual and global horizontal pleiotropy in Mendelian randomization—a job for the humble heterogeneity statistic? 2018;187(12):2681–5. PubMed PMC

Zheng J, Baird D, Borges M-C, Bowden J, Hemani G, Haycock P, et al. Recent developments in Mendelian randomization studies. Curr Epidemiol Rep. 2017;4(4):330–345. doi: 10.1007/s40471-017-0128-6. PubMed DOI PMC

Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Statistic Soc: Series B (Methodological) 1995;57(1):289–300.

Sanderson E, Davey Smith G, Windmeijer F, Bowden J. An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. Int J Epidemiol. 2018;dyy262:1–15. PubMed PMC

Kujala UM, Mäkinen V-P, Heinonen I, Soininen P, Kangas AJ, Leskinen TH, et al. Long-term leisure-time physical activity and serum metabolome. Circulation. 2012:CIRCULATIONAHA. 112.105551. PubMed

Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197–206. doi: 10.1038/nature14177. PubMed DOI PMC

Shungin D, Winkler TW, Croteau-Chonka DC, Ferreira T, Locke AE, Mägi R, et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature. 2015;518(7538):187–196. doi: 10.1038/nature14132. PubMed DOI PMC

Sanderson E, Spiller W, Bowden J. Testing and correcting for weak and pleiotropic instruments in two-sample multivariable Mendelian randomisation. BioRxiv. 2020. 10.1101/2020.04.02.021980. PubMed PMC

Murphy N, Jenab M, Gunter MJ. Adiposity and gastrointestinal cancers: epidemiology, mechanisms and future directions. Nat Rev Gastroenterol Hepatol. 2018;15:659–670. doi: 10.1038/s41575-018-0038-1. PubMed DOI

Wells JC. Sexual dimorphism of body composition. Best Pract Res Clin Endocrinol Metab. 2007;21(3):415–430. doi: 10.1016/j.beem.2007.04.007. PubMed DOI

Lovejoy J, Champagne C, De Jonge L, Xie H, Smith S. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes. 2008;32(6):949–958. doi: 10.1038/ijo.2008.25. PubMed DOI PMC

Bell JA, Carslake D, O’Keeffe LM, Frysz M, Howe LD, Hamer M, et al. Associations of body mass and fat indexes with cardiometabolic traits. J Am Coll Cardiol. 2018;72(24):3142–3154. doi: 10.1016/j.jacc.2018.09.066. PubMed DOI PMC

Flegal KM, Shepherd JA, Looker AC, Graubard BI, Borrud LG, Ogden CL, et al. Comparisons of percentage body fat, body mass index, waist circumference, and waist-stature ratio in adults. Am J Clin Nutr. 2009;89(2):500–508. doi: 10.3945/ajcn.2008.26847. PubMed DOI PMC

Wei H-J, Zeng R, Lu J-H, Lai W-FT, Chen W-H, Liu H-Y, et al. Adipose-derived stem cells promote tumor initiation and accelerate tumor growth by interleukin-6 production. Oncotarget. 2015;6:7713–7726. doi: 10.18632/oncotarget.3481. PubMed DOI PMC

Hotamisligil G. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–867. doi: 10.1038/nature05485. PubMed DOI

Rinaldi S, Cleveland R, Norat T, Biessy C, Rohrmann S, Linseisen J, et al. Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies. Int J Cancer. 2010;126:NA-NA. PubMed

Tran TT, Naigamwalla D, Oprescu AI, Lam L, McKeown-Eyssen G, Bruce WR, et al. Hyperinsulinemia, but not other factors associated with insulin resistance, acutely enhances colorectal epithelial proliferation in vivo. Endocrinol. 2006;147:1830–1837. doi: 10.1210/en.2005-1012. PubMed DOI

Kiunga GA, Raju J, Sabljic N, Bajaj G, Good CK, Bird RP. Elevated insulin receptor protein expression in experimentally induced colonic tumors. Cancer Lett. 2004;211:145–153. doi: 10.1016/j.canlet.2004.02.015. PubMed DOI

Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, et al. Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst. 2000;92:1592–1600. doi: 10.1093/jnci/92.19.1592. PubMed DOI

Murphy N, Carreras-Torres R, Song M, Chan AT, Martin RM, Papadimitriou N, et al. Circulating levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 associate with risk of colorectal cancer based on serologic and Mendelian randomization analyses. Gastroenterology. 2019;158(5):1300–312.e20. 10.1053/j.gastro.2019.12.020. PubMed PMC

Burgess S, Thompson SG, CRP CHD Genetics Collaboration. Avoiding bias from weak instruments in Mendelian randomization studies. International Journal of Epidemiology 2011;40(3):755–64. PubMed

Gonzalez EC, Roetzheim RG, Ferrante JM, Campbell R. Predictors of proximal vs. distal colorectal cancers. Dis Colon Rectum. 2001;44:251–258. doi: 10.1007/BF02234301. PubMed DOI

Jacobs ET, Thompson PA, Martínez MaE. Diet, gender, and colorectal neoplasia. J Clin Gastroenterol 2007;41:731–746. PubMed

Okubo R, Masuda H, Nemoto N. p53 mutation found to be a significant prognostic indicator in distal colorectal cancer. Oncol Rep. 2001;8(3):509-14. PubMed

Pekow J, Meckel K, Dougherty U, Butun F, Mustafi R, Lim J, et al. Tumor suppressors miR-143 and miR-145 and predicted target proteins API5, ERK5, K-RAS, and IRS-1 are differentially expressed in proximal and distal colon. Am J Physiol-Gastrointestinal Liver Physiol. 2015;308:G179–GG87. doi: 10.1152/ajpgi.00208.2014. PubMed DOI PMC

Missiaglia E, Jacobs B, D’Ario G, Di Narzo AF, Soneson C, Budinska E, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol. 2014;25:1995–2001. doi: 10.1093/annonc/mdu275. PubMed DOI

Dale KM, Coleman CI, Henyan NN, Kluger J, White CM. Statins and cancer risk: a meta-analysis. JAMA. 2006;295(1):74–80. doi: 10.1001/jama.295.1.74. PubMed DOI

Liu Y, Tang W, Wang J, Xie L, Li T, He Y, et al. Association between statin use and colorectal cancer risk: a meta-analysis of 42 studies. Cancer Causes Control. 2014;25(2):237–49. PubMed

Lytras T, Nikolopoulos G, Bonovas S. Statins and the risk of colorectal cancer: An updated systematic review and meta-analysis of 40 studies. World J Gastroenterol. 2014;20(7):1858–70. PubMed PMC

Yao X, Tian Z. Dyslipidemia and colorectal cancer risk: a meta-analysis of prospective studies. Cancer Causes Control. 2015;26(2):257–268. doi: 10.1007/s10552-014-0507-y. PubMed DOI

Lee S, Zhang C, Kilicarslan M, Piening BD, Bjornson E, Hallström BM, et al. Integrated network analysis reveals an association between plasma mannose levels and insulin resistance. Cell Metab. 2016;24(1):172–184. doi: 10.1016/j.cmet.2016.05.026. PubMed DOI PMC

Lawlor DA, Tilling K, Davey SG. Triangulation in aetiological epidemiology. Int J Epidemiol. 2016;45(6):1866–1886. PubMed PMC

Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol. 2016;40(7):597–608. doi: 10.1002/gepi.21998. PubMed DOI PMC

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