How Might Body Fat Distribution Affect Cancer Risk?
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Where Body Fat Is Stored May Determine Cancer Risk
Obesity is a well-established risk factor for many cancers, particularly breast, colorectal (bowel), liver, and endometrial (uterine lining) cancers. Scientists now emphasize that assessing total fat alone (for example, with body mass index—BMI) may be insufficient. Modern epidemiological and genetic methods show that how fat is distributed in the body is at least as important as total fat in determining cancer risk.
In 2025, the Journal of the National Cancer Institutepublished a comprehensive study using Mendelian randomization to systematically assess potential causal links between five different fat-distribution traits and 12 obesity-related cancers .
Is BMI Alone Enough?
For years, body mass index (BMI)has been the main measure of overweight and obesity. Because excess weight is linked to several cancers, clinicians often use BMI to assess risk.
This new study suggests BMI may be insufficient on its own to predict cancer risk . According to the research, where fat is stored in the bodymay be at least as important as BMI.
Study Aim
The main aim was to examine the causal effects of these five fat-distribution traits:
- Abdominal subcutaneous adipose tissue (ASAT): Fat beneath the abdominal skin
- Visceral adipose tissue (VAT): Fat surrounding internal organs
- Gluteofemoral adipose tissue (GFAT): Fat around the hips and thighs
- Liver fat
- Pancreatic fat
Cancers examined included endometrial, ovarian, breast, colorectal, pancreatic, multiple myeloma, liver, kidney, thyroid, gallbladder, esophageal adenocarcinoma, and meningioma.
Design and Methods
Rather than a direct clinical cohort, this was a genome-wide association study (GWAS) summary-data-based Mendelian randomization (MR) analysis.
- Design: Two-sample MR; genetic variants used as instrumental variables.
- Exposure: Independent GWAS data for ASAT, VAT, GFAT, liver fat, and pancreatic fat.
- Outcome: Risk changes in 12 cancer types.
- Analysis: Estimated risk change, expressed as an odds ratio, per standard-deviation increase in each fat trait.
- Mediation Analysis: Tested the effects of hormonal and metabolic markers such as insulin and SHBG.
Findings: Fat Distribution and Cancer Risk
| Fat-Distribution Trait | Risk ↑ (Increase) | Risk ↓ (Decrease/Protective) | Brief Explanation |
|---|---|---|---|
| ASAT | Endometrial, esophageal adenocarcinoma, liver | Breast (some subtypes) | More abdominal subcutaneous fat increased risk; breast cancer findings were heterogeneous. |
| VAT | Liver cancer | — | Fat around internal organs is associated with inflammation and metabolic stress. |
| Liver fat | Liver cancer | — | Strong association between hepatic fat accumulation and hepatocellular carcinoma. |
| GFAT | — | Breast, meningioma | Hip–thigh fat showed a protective signal in some cancers. |
| Pancreatic fat | Uncertain | — | Insufficient evidence; further studies needed. |
Clinical Implications and Limitations
- BMI is not enough: Considering fat distribution may improve risk assessment accuracy.
- Central obesity is critical: ASAT, VAT, and liver fat provide important risk signals, particularly for liver and endometrial cancers.
- GFAT and protective effects: Hip and thigh fat stores may reduce risk in some cancers by diverting metabolic stress.
- Limitations: MR approaches causality but does not eliminate bias completely. The population was predominantly of European ancestry, and statistical power may be limited for some cancer subtypes.
Conclusion
This comprehensive genetic analysis shows that fat distribution plays a critical role in determining cancer risk . Researchers emphasize that fat-distribution measurements should be considered in obesity management and cancer-prevention strategies.
"Assessing changes in fat distribution could become an important tool in obesity treatment and cancer prevention."
References
- Hazelwood E, et al. Adiposity distribution and risks of 12 obesity-related cancers: a Mendelian randomization analysis. JNCI. 2025. doi:10.1093/jnci/djaf201
- Hazelwood E, et al. Adiposity distribution and risks of twelve obesity-related cancers (preprint). medRxiv. 2025. doi:10.1101/2025.01.10.25320324
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