2025/09/12 by Emma Hazelwood, Lucy J. Goudswaard, Matthew A. Lee +18 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Adipokines, Inflammation, and Metabolic Diseases #Cardiovascular Disease and Adiposity #Genetic Associations and Epidemiology
paper · pdf · doi:10.1093/jnci/djaf201
openalex publication_date 2025/09/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
INTRODUCTION: There is convincing evidence that overall adiposity increases the risks of several cancers. Whether the distribution of adiposity plays a similar role is unclear. METHODS: 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). RESULTS: 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). DISCUSSION: 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.