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

Hazelwood, E; Goudswaard, LJ; Lee, MA; Vabistsevits, M; Pournaras, DJ; Brenner, H; Buchanan, DD; Gruber, SB; Gsur, A; Li, L; Vodickova, L; Grant, RC; Samadder, NJ; Timpson, NJ; Gunter, MJ; Schuster-Böckler, B; Yarmolinsky, J; Richardson, TG; Freisling, H; Murphy, N; Vincent, EE

Women's Health Collection

Journal article

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

Abstract:: 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.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Hazelwood, E., Goudswaard, L. J., Lee, M. A., Vabistsevits, M., Pournaras, D. J., Brenner, H., 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., … Vincent, E. E. (2025). Adiposity distribution and risks of 12 obesity-related cancers: a Mendelian randomization analysis. Journal of the National Cancer Institute, 117(12), 2621–2642.

MLA Style

Hazelwood, E, et al. “Adiposity Distribution and Risks of 12 Obesity-Related Cancers: a Mendelian Randomization Analysis.” Journal of the National Cancer Institute, vol. 117, no. 12, 2025, pp. 2621–42.

Chicago Style

Hazelwood, E, LJ Goudswaard, MA Lee, et al. 2025. “Adiposity Distribution and Risks of 12 Obesity-Related Cancers: a Mendelian Randomization Analysis.” Journal of the National Cancer Institute 117 (12): 2621–42.
Print