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Adiposity distribution and risks of 12 obesity-related cancers: a Mendelian randomization analysis

There is convincing evidence that overall adiposity increases the risks of several cancers. Whether the distribution of adiposity plays a similar role is unclear.We used 2-sample Mendelian randomization (MR) to examine causal relationships of 5 adiposity distribution traits (abdominal subcutaneous a...

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Main Authors: Hazelwood, Emma (Author) , Goudswaard, Lucy J (Author) , Lee, Matthew A (Author) , Vabistsevits, Marina (Author) , Pournaras, Dimitri J (Author) , Brenner, Hermann (Author) , Buchanan, Daniel D (Author) , Gruber, Stephen B (Author) , Gsur, Andrea (Author) , Li, Li (Author) , Vodickova, Ludmila (Author) , Grant, Robert C (Author) , Samadder, N Jewel (Author) , Timpson, Nicholas J (Author) , Gunter, Marc J (Author) , Schuster-Böckler, Benjamin (Author) , Yarmolinsky, James (Author) , Richardson, Tom G (Author) , Freisling, Heinz (Author) , Murphy, Neil (Author) , Vincent, Emma E (Author)
Format: Article (Journal)
Language:English
Published: September 24, 2025
In: Journal of the National Cancer Institute
Year: 2025, Volume: 117, Issue: 12, Pages: 2621-2642
ISSN:1460-2105
DOI:10.1093/jnci/djaf201
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1093/jnci/djaf201
Verlag, kostenfrei, Volltext: https://academic.oup.com/jnci/article/117/12/2621/8262518?login=true
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Author Notes:Emma Hazelwood, PhD, Lucy J Goudswaard, PhD, Matthew A Lee, PhD, Marina Vabistsevits, PhD, Dimitri J Pournaras, MD, PhD, Hermann Brenner, MD, MPH, Daniel D Buchanan, PhD, Stephen B Gruber, MD, PhD, MPH, Andrea Gsur, PhD, Li Li, MD, PhD, Ludmila Vodickova, MD, PhD, Robert C Grant, PhD, N Jewel Samadder, MD, Nicholas J Timpson, PhD, Marc J Gunter, PhD, Benjamin Schuster-Böckler, PhD, James Yarmolinsky, PhD, Tom G Richardson, PhD, Heinz Freisling, PhD, Neil Murphy, PhD, Emma E Vincent, PhD
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Summary:There is convincing evidence that overall adiposity increases the risks of several cancers. Whether the distribution of adiposity plays a similar role is unclear.We used 2-sample Mendelian randomization (MR) to examine causal relationships of 5 adiposity distribution traits (abdominal subcutaneous adipose tissue (ASAT); visceral adipose tissue (VAT); gluteofemoral adipose tissue (GFAT); liver fat; and pancreas fat) with the risks of 12 obesity-related cancers (endometrial, ovarian, breast, colorectal, pancreas, multiple myeloma, liver, kidney (renal cell), thyroid, gallbladder, esophageal adenocarcinoma, and meningioma).Sample size across all genome-wide association studies (GWAS) ranged from 8407 to 728896 (median: 57249). We found evidence that higher genetically predicted ASAT increased the risks of endometrial cancer, liver cancer, and esophageal adenocarcinoma (odds ratios (OR) and 95% confidence intervals (CI) per standard deviation (SD) higher ASAT = 1.79 (1.18 to 2.71), 3.83 (1.39 to 10.53), and 2.34 (1.15 to 4.78), respectively). Conversely, we found evidence that higher genetically predicted GFAT decreased the risks of breast cancer and meningioma (ORs and 95% CIs per SD higher genetically predicted GFAT = 0.77 (0.62 to 0.97) and 0.53 (0.32 to 0.90), respectively). We also found evidence for an effect of higher genetically predicted VAT and liver fat on increased liver cancer risk (ORs and 95% CIs per SD higher genetically predicted adiposity trait = 4.29 (1.41 to 13.07) and 4.09 (2.29 to 7.28), respectively).Our analyses provide novel insights into the relationship between adiposity distribution and cancer risk. These insights highlight the potential importance of adipose tissue distribution alongside maintaining a healthy weight for cancer prevention.
Item Description:Gesehen am 19.02.2026
Physical Description:Online Resource
ISSN:1460-2105
DOI:10.1093/jnci/djaf201

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