Cancer risk is affected by where fat is stored in the body

Where your body stores fat may matter as much as how much fat you carry when it comes to certain cancers. A new analysis finds that fat distribution across the body can change cancer risk, and the pattern is not the same for every cancer type.

Researchers from several countries, led by a team at the University of Bristol, looked beyond body mass index to see whether fat in specific regions – arms and legs, trunk, and the visceral fat wrapped around internal organs – plays a different role than overall size.

The research adds weight to calls for more precise ways to assess obesity-related health risks.

Testing fat’s role in cancer

Scientists already know that obesity raises the risk of multiple cancers. Most of that evidence uses BMI as the yardstick. But BMI is blunt. It can’t tell a muscular frame from excess fat, and it can’t show where fat sits.

Heart research has shown for years that central, visceral fat is especially harmful. Whether similar rules apply to cancer has been less clear.

The Bristol team set out to test this idea across 12 obesity-related cancers. These include endometrial, ovarian, and breast cancers, as well as colorectal, pancreatic, multiple myeloma, liver, kidney (renal cell), thyroid, gallbladder, esophageal adenocarcinoma, and meningioma.

The question was simple but ambitious: Does fat in different places alter risk in different ways?

Fat distribution matters differently

The researchers applied Mendelian randomization, a method that uses naturally occurring genetic variants influencing where people store fat as proxies for lifelong exposure.

Since genes are fixed at conception, this approach helps distinguish cause from mere correlation in large health datasets.

Fat distribution appears to matter – but not uniformly. For some cancers, the location of fat seems more important than total fat. For others, total fat matters more than where it sits. In a few, both play a role.

When distribution does matter, the body regions that drive risk differ from cancer to cancer. That patchwork points to different biological pathways linking fat to tumors across tissues.

“These findings support the growing consensus that BMI, while useful for population-level trends, may be too simplistic for assessing individual health risks,” said study lead author Emma Hazelwood, who conducted her PhD at Bristol.

“Our results tell us that there is no ‘one-size-fits-all’ when it comes to cancer, meaning a more tailored approach to cancer prevention in people with obesity could be most effective.”

Targeting fat patterns in cancer

BMI captures size, not shape. Two people can share a BMI and have very different health profiles if one carries more visceral fat deep in the abdomen and the other stores more subcutaneous fat under the skin.

The study’s results echo recent frameworks from leading obesity groups that call BMI a flawed diagnostic tool and urge clinicians to look at body composition and fat patterning.

If certain fat depots drive risk for particular cancers, prevention can get smarter. Imaging, waist-to-hip ratio, and emerging blood markers might help flag people who most need tailored screening or early intervention.

Understanding the biological mechanisms

Treatments for obesity – lifestyle, medications, and procedures – could be chosen and evaluated not just by weight loss, but by how they shift harmful fat stores. Biology also matters. Hormones, inflammation, insulin signaling, and immune activity differ by fat depot.

That could explain why ovarian cancer might respond to one fat pattern while colorectal cancer responds to another. Understanding those pathways could reveal new targets for drugs and prevention.

“It is vital to understand the biological mechanisms that underpin these associations – particularly how and why different fat depots affect cancer development,” Hazelwood said.

“In the longer term, we need to explore how obesity treatments – whether lifestyle- or drug-based – influence these risk pathways.”

A new look at cancer prevention

The work relies on large genetic datasets that are still dominated by people of European ancestry. The team recommends follow-up studies using different methods and more diverse populations.

Julia Panina of the World Cancer Research Fund noted that the research highlights the role of maintaining a healthy weight to reduce cancer risk.

“While this remains essential, growing scientific evidence shows that body composition – particularly how fat is distributed throughout the body – is also a crucial factor,” said Panina.

“With support from our fantastic donors, we were able to co-fund the University of Bristol’s excellent team whose findings will help direct this exciting area towards possible new cancer prevention and treatments.”

The research was published in the Journal of the National Cancer Institute.

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