Journal Article

DKFZ-2025-01949

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Adiposity distribution and risks of 12 obesity-related cancers: a Mendelian randomization analysis.

Hazelwood, E. ; Goudswaard, L. J. ; Lee, M. A. ; Vabistsevits, M. ; Pournaras, D. J. ; Brenner, H.DKFZ* ; Buchanan, D. D. ; Gruber, S. B. ; Gsur, A. ; Li, L. ; Vodickova, L. ; Grant, R. C. ; Samadder, N. J. ; Timpson, N. J. ; Gunter, M. J. ; Schuster-Böckler, B. ; Yarmolinsky, J. ; Richardson, T. G. ; Freisling, H. ; Murphy, N. ; Vincent, E. E.

2025
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/jnci/djaf201

Abstract: 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 728 896 (median: 57 249). 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.

Note: 2025 Dec 1;117(12):2621-2642

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Contributing Institute(s):

1. C070 Klinische Epidemiologie der Krebsfrüherkennung (C070)
2. Primäre Krebsprävention (C120)
3. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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