Metabolic abnormalities increase obesity-related cancer risk

In one of the first studies to examine this metabolically unhealthy phenomenon obesity is associated with an increased risk, approximately 1.5 times higher, of any obesity-related cancer, and with an even higher risk, two to three times higher, for specific cancers, such as cancers of the endometrium, liver and kidney cells, compared with a metabolically healthy normal weight.

Even in people with so-called “metabolically healthy” obesity, the overall obesity-related cancer risk is increased compared to normal-weight, metabolically healthy individuals; however, the associations here are weaker than in people with metabolically unhealthy obesity.

“The type of metabolic obesity phenotype is important when assessing obesity-related cancer risk,” said lead researcher Ming Sun, PhD, of Lund University, Malmö, Sweden. Medscape Medical News. “In general, metabolic aberrations further increased obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.”

“This synergy means that when obesity and metabolic disease occur together, it’s particularly bad,” added lead author Tanja Stocks, PhD, also from Lund University.

“But the data also underscores that even obesity and being overweight alone represent an increased risk of cancer,” Stock noted.

Sun said the findings have important implications for public health, suggesting that “significant numbers of cancer cases could potentially be prevented by targeting the coexistence of metabolic problems and obesity, especially for cancers linked to obesity in men.

The results will be presented as a poster by Sun at the European Obesity Congress (ECO) 2023, to be held in Dublin, Ireland, and have been published in the Journal of the National Cancer Institute.

Metabolically unhealthy obesity is the worst cancer risk

Andrew G. Renehan, PhD, FRCS, Professor of Cancer Studies and Surgery, University of Manchester, UK, welcomed the new work, saying it solves the problem with a huge number of studies. “[It] well demonstrates that there are clear examples where the metabolically unhealthy overweight and obese phenotypes have an increased risk of cancer compared to [metabolically] healthy overweight and obese phenotypes,” he said.

“There is a clear need for clinical research addressing these hypotheses…but these studies will additionally need to consider other dimensions such as the selection of treatment for metabolic aberrations, both medical and surgical, and the resulting metabolic control interventions,” Renehan observed.

Vibhu Chittajallu, MD, gastroenterologist based in University Hospitals Cleveland Medical Center, Ohio, said it was beneficial to see another study further validate the association of obesity with the development of obesity-associated cancers.

“It’s an interesting study. [because it focuses] on the role of metabolic syndrome in obesity and how it affects the risk of developing cancers associated with obesity,” he said. Medscape Medical News.

“I believe the results of this study further reinforce the need for improved management of obesity and metabolic syndrome to reduce the risk of obesity-associated cancer formation that plays a role in preventable and premature deaths. in obese adult patients.

Synergy between metabolic aberrations and obesity, and cancer risk

Sun and his colleagues note that obesity is an established risk factor for several cancers. It is often accompanied by metabolic aberrations, which has been a commonly proposed mechanism to link obesity to cancer. Over the past decade, obesity with or without metabolic aberrations – commonly referred to as “metabolically unhealthy obesity” or “healthy obesity” – has been widely studied in the cardiovascular field; however, studies regarding cancer are limited.

According to Sun, this new study is the first to examine the synergistic effect of unhealthy metabolism and body mass index (BMI) – the latter was later categorized as normal weight (BMI < 25 kg/m²), overweight (BMI < 30 kg/m²) and obesity (BMI ≤ 30 kg/m²)—and the association with cancer risk, both overall and with respect to site-specific cancers.

The data was drawn from 797,193 European individuals (in Norway, Sweden and Austria), of whom 23,630 developed obesity-related cancer during the follow-up period. A metabolic score including mean blood pressure, blood glucose and triglycerides was used to provide a measure of healthy or unhealthy metabolic status. Relative risks (hazard ratios, RR) for global and site-specific cancers were determined. Comparisons were made with metabolically healthy people of normal weight (actually controls).

When different metabolic scores and BMI were combined, participants fell into six categories: metabolically unhealthy obesity (6.8% of participants); metabolically healthy obesity (3.4%), metabolically unhealthy overweight (15.4%), metabolically healthy overweight (19.8%), metabolically unhealthy normal weight (12.5%) and metabolically healthy normal weight (42.0% ).

Metabolically unhealthy obese women had a relative risk (HR) of 1.43 for all obesity-related cancers, compared to metabolically healthy women of normal weight. Of particular note are the risks of two types of cancer in women with unhealthy metabolic obesity: kidney cancer, with an RR of 2.43, and endometrial cancerwith an HR of 3.0, compared to controls.

Even in metabolically healthy obese women (compared to metabolically healthy women of normal weight), there was an increased risk of endometrial cancer, with an HR of 2.36.

“If you look at individual cancers, especially endometrial cancer, it seems to be very much related to obesity and not so much to the metabolic factor,” Stocks noted..

In men, compared to metabolically healthy, normal-weight men, metabolically unhealthy and obese men had an overall obesity-related cancer risk of 1.91 HR. More specifically, the risk of kidney cell cancer more than doubled, with an HR of 2.59. HR for Colon Cancer was 1.85, and that for rectal cancer And pancreatic cancer was similar, with both having HRs of 1.32.

Again, the risk was lower in metabolically healthy obese men, although it was still higher than in metabolically healthy, normal-weight men.

European Obesity Congress (ECO) 2023. Abstract P2.027. Presented Friday, May 19, 2023.

Sun, Stocks, Chitajallu and Renehan did not report any relevant financial relationships.

J Natl Cancer Inst. 2023;115:456-467. Full Text

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