Friday, December 1, 2023
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Obesity is an established risk factor for several cancers, often accompanied by metabolic aberrations thought to underlie that increased risk. The metabolic syndrome, encompassing obesity and metabolic aberrations, is linked to increased risk for some obesity-related cancers, including pancreatic, postmenopausal breast, liver, colorectal, endometrial, and renal cell cancer.
A meta-analysis published in 2020 showed increased cancer risk among metabolically healthy obese individuals, but it was based on only 7 studies of different cancers. A recent prospective study suggested that the impact of obesity on cancer risk varies by metabolic health status and cancer type, but more evidence is needed for specific cancers.
In 1 of the first studies to examine this phenomenon, metabolically unhealthy obesity is associated with an increased risk--around 1.5-fold higher--for any obesity-related cancer, and an even higher risk--2- to 3-fold higher--for specific cancers, such as endometrial, liver, and renal cell cancers, compared with metabolically healthy normal weight.
Even in people with so-called “metabolically healthy” obesity, the risk for overall obesity-related cancer is increased compared with 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,” lead researcher Ming Sun, PhD, from Lund University, Malmö, Sweden, told Medscape Medical News. “In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.”
“This synergy means that when obesity and metabolic unhealth occur together, that’s particularly bad,” added Tanja Stocks, PhD, senior author, also of Lund University.
“But the data also highlight that even obesity and overweight alone comprise an increased risk of cancer,” Dr Stocks noted.
Dr Sun said that the findings have important public health implications, suggesting that ”a significant number of cancer cases could potentially be prevented by targeting the coexistence of metabolic problems and obesity, in particular for obesity-related cancers among men.”
The results were presented as a poster by Dr Sun at the European Congress on Obesity (ECO) 2023, in Dublin, Ireland, and were published in the Journal of the National Cancer Institute.
Metabolically Unhealthy Obesity Worst for Cancer Risks
Andrew G. Renehan, PhD, professor of cancer studies and surgery, University of Manchester, United Kingdom, welcomed the new work, saying that it addresses the issue with very large study numbers. “[It] nicely demonstrates that there are clear examples where metabolically unhealthy overweight and obese phenotypes have increased cancer risk relative to [metabolically] healthy overweight and obese phenotypes,” he said.
“There is a clear need for clinically based research addressing these hypotheses. . . but these studies will additionally need to factor in other dimensions such as the selection of treatment for metabolic aberrations, both medical and surgical, and the consequent metabolic control resulting from these interventions,” Dr Renehan observed.
Vibhu Chittajallu, MD, a gastroenterologist based atUniversity Hospitals Cleveland Medical Center, Ohio, said that it was beneficial to see another study further validating the association of obesity with the development of obesity-associated cancers.
“This is an interesting study [because it focuses] on the role of metabolic syndrome in obesity and how it affects the risk of development of obesity-associated cancers,” he told Medscape Medical News.
“I believe that the results of this study further strengthen 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 adult patients with obesity.”
Synergy Between Metabolic Aberrations and Obesity, and Cancer Risk
Dr Sun and colleagues note that obesity is an established risk factor for several cancers. It is often accompanied by metabolic aberrations, which have been a commonly proposed mechanism to link obesity to cancer. During the last decade, obesity with or without metabolic aberrations, commonly termed “metabolically unhealthy” or “healthy obesity,” respectively, has been extensively investigated in the cardiovascular field; however, studies regarding cancer are limited.
According to Dr Sun, this new study is the first to look at the synergistic effect of unhealthy metabolism and body mass index (BMI)--the latter was further 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 in relation to site-specific cancers.
Data were drawn from 797,193 European individuals (in Norway, Sweden, and Austria), of whom 23,630 developed an obesity-related cancer during the follow-up period. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to provide a measure of healthy or unhealthy metabolic status. Relative risks (hazard ratios, HRs) for overall and site-specific cancers were determined. Comparisons were made with metabolically healthy people of normal weight (effectively controls).
When different metabolic scores and BMIs were combined, participants fell into 6 categories: metabolically unhealthy obesity (6.8% of participants), metabolically healthy obesity (3.4%), metabolically unhealthy overweight (15.4%), metabolically healthy overweight (19.9%), metabolically unhealthy normal weight (12.5%), and metabolically healthy normal weight (42.0%).
Metabolically unhealthy women with obesity had aHR of 1.43 for overall obesity-related cancers compared with metabolically healthy women of normal weight. Of particular note were risks for 2 cancer types in women with metabolically unhealthy obesity: renal cancer, with an HR of 2.43, and endometrial cancer, with an HR of 3.00, compared with controls.
Even in metabolically healthy women with obesity (compared with metabolically healthy women of normal weight), there was an increased risk for endometrial cancer, with an HR of 2.36.
“If you look at individual cancers, [and] in particular endometrial cancer, this seems to be very much driven by obesity and not so much by the metabolic factor,” remarked Dr Stocks.
In men, compared with metabolically healthy men of normal weight, metabolically unhealthy men with obesity had an overall obesity-related cancer risk of HR 1.91. Specifically, the risk for renal cell cancer was more than doubled, with an HR of 2.59. The HR for colon cancer was 1.85, and that for rectal cancer and pancreatic cancer was similar, with both conditions having an HR of 1.32.
Again, risk was lower in metabolically healthy men with obesity, although it was still higher than for metabolically healthy normal-weight men.
Sun, Stocks, Chitajallu, and Renehan have reported no relevant financial relationships.
European Congress on Obesity (ECO) 2023. Abstract P2.027. Presented Friday, May 19, 2023.
J Natl Cancer Inst. 2023;115:456-467.[1]
