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| 001 | 298202 | ||
| 005 | 20250124163420.0 | ||
| 024 | 7 | _ | |a 10.1093/ije/dyae175 |2 doi |
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| 024 | 7 | _ | |a 0300-5771 |2 ISSN |
| 024 | 7 | _ | |a 1464-3685 |2 ISSN |
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| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Lee, Matthew A |0 0000-0001-6262-3447 |b 0 |
| 245 | _ | _ | |a A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator. |
| 260 | _ | _ | |a Oxford |c 2025 |b Oxford Univ. Press |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1737729326_25370 |2 PUB:(DE-HGF) |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Adiposity is an established risk factor for colorectal cancer (CRC). The pathways underlying this relationship, and specifically the role of circulating proteins, are unclear.Utilizing two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable associations between: (i) body mass index (BMI) and waist-hip ratio (WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (ii) BMI and WHR and circulating proteins, and (iii) adiposity-associated circulating proteins and CRC risk. We used MVMR to investigate the potential mediating role of adiposity- and CRC-related circulating proteins in the adiposity-CRC association.BMI and WHR were positively associated with CRC risk, with similar associations by anatomical tumor site. In total, 6591 adiposity-protein (2628 unique circulating proteins) and 33 protein-CRC (7 unique circulating proteins) associations were identified using UVMR and colocalization. One circulating protein, GREM1, was associated with BMI (only) and CRC outcomes in a manner that was consistent with a potential mediating role in sex-combined and female-specific analyses. In MVMR, adjusting the BMI-CRC association for GREM1, effect estimates were attenuated-suggestive of a potential mediating role-most strongly for the BMI-overall CRC association in women.Results highlight the impact of adiposity on the plasma proteome and of adiposity-associated circulating proteins on the risk of CRC. Supported by evidence from UVMR and colocalization analyses using cis-single-nucleotide polymorphisms, GREM1 was identified as a potential mediator of the BMI-CRC association, particularly in women. |
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| 650 | _ | 7 | |a Mendelian randomization |2 Other |
| 650 | _ | 7 | |a adiposity |2 Other |
| 650 | _ | 7 | |a colocalization |2 Other |
| 650 | _ | 7 | |a colorectal cancer |2 Other |
| 650 | _ | 7 | |a proteome |2 Other |
| 650 | _ | 7 | |a GREM1 protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a Intercellular Signaling Peptides and Proteins |2 NLM Chemicals |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Adiposity: genetics |2 MeSH |
| 650 | _ | 2 | |a Colorectal Neoplasms: genetics |2 MeSH |
| 650 | _ | 2 | |a Colorectal Neoplasms: epidemiology |2 MeSH |
| 650 | _ | 2 | |a Body Mass Index |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a Male |2 MeSH |
| 650 | _ | 2 | |a Mendelian Randomization Analysis |2 MeSH |
| 650 | _ | 2 | |a Waist-Hip Ratio |2 MeSH |
| 650 | _ | 2 | |a Risk Factors |2 MeSH |
| 650 | _ | 2 | |a Intercellular Signaling Peptides and Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a Obesity: genetics |2 MeSH |
| 650 | _ | 2 | |a Proteomics |2 MeSH |
| 650 | _ | 2 | |a Polymorphism, Single Nucleotide |2 MeSH |
| 700 | 1 | _ | |a Hatcher, Charlie A |b 1 |
| 700 | 1 | _ | |a Hazelwood, Emma |b 2 |
| 700 | 1 | _ | |a Goudswaard, Lucy J |b 3 |
| 700 | 1 | _ | |a Tsilidis, Konstantinos K |b 4 |
| 700 | 1 | _ | |a Vincent, Emma E |b 5 |
| 700 | 1 | _ | |a Martin, Richard M |b 6 |
| 700 | 1 | _ | |a Smith-Byrne, Karl |b 7 |
| 700 | 1 | _ | |a Brenner, Hermann |0 P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2 |b 8 |u dkfz |
| 700 | 1 | _ | |a Cheng, Iona |0 0000-0003-4132-2893 |b 9 |
| 700 | 1 | _ | |a Kweon, Sun-Seog |b 10 |
| 700 | 1 | _ | |a Le Marchand, Loic |b 11 |
| 700 | 1 | _ | |a Newcomb, Polly A |b 12 |
| 700 | 1 | _ | |a Schoen, Robert E |0 0000-0001-7153-2766 |b 13 |
| 700 | 1 | _ | |a Peters, Ulrike |b 14 |
| 700 | 1 | _ | |a Gunter, Marc J |b 15 |
| 700 | 1 | _ | |a Van Guelpen, Bethany |0 0000-0002-9692-101X |b 16 |
| 700 | 1 | _ | |a Murphy, Neil |0 0000-0003-3347-8249 |b 17 |
| 773 | _ | _ | |a 10.1093/ije/dyae175 |g Vol. 54, no. 1, p. dyae175 |0 PERI:(DE-600)1494592-7 |n 1 |p dyae175 |t International journal of epidemiology |v 54 |y 2025 |x 0300-5771 |
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