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Metabolically healthy and unhealthy obesity increases risk of obesity-related cancers

Updated: May 18, 2023

Metabolically healthy and unhealthy 'forms' of obesity are associated with an increased risk of various obesity-related cancers, with the relationship stronger in metabolically unhealthy obesity, according to a study by researchers from Lund University, Malmö, Sweden, presented at the European Congress on Obesity in Dublin, Ireland, and published in the Journal of the National Cancer Institute (Metabolically (un)healthy obesity and risk of obesity-related cancers: a pooled study).

Led by Dr Ming Sun from Lund University, they investigated body mass index (BMI, normal weight/overweight/obesity) jointly and in interaction with metabolic health status in relation to obesity-related cancer risk (n=23,630) among 797,193 European individuals. A metabolic score comprising blood pressure, plasma glucose and triglycerides (blood fats) was used to define metabolically healthy and unhealthy status, and statistical modelling was used to estimate any relationship.

The participants were put into six different categories: metabolically unhealthy obesity (6.8% of participants); metabolically healthy obesity (3.4%), metabolically unhealthy overweight (15.4%), metabolically health overweight (19.8%), metabolically unhealthy normal weight (12.5%) and metabolically healthy normal weight (42.0%).

Metabolically unhealthy obesity, was, compared to metabolically healthy normal weight, associated with an increased relative risk of any obesity-related cancer and colon, rectal, pancreas, endometrial, liver, gallbladder, and renal cell cancer, with the highest risk estimates for endometrial, liver, and renal cell cancer (2.5 to 3.0 times increased risk).

In women, compared to metabolically healthy women of normal weight, metabolically unhealthy women with obesity had a 21% increased risk of colon cancer, a 3-times increased risk of endometrial cancer, and a 2.5 times increased risk of kidney cancer. Metabolically healthy women with obesity had a 2.4 times increased risk of endometrial cancer and an 80% increased risk of kidney cancer—but the relationship with colon cancer was no longer statistically significant.

In men, compared to metabolically healthy men of normal weight, metabolically unhealthy men with obesity had a 2.6 times increased risk of kidney cancer, an 85% increased risk of colon cancer, and a 32% increased risk of both pancreatic and rectal cancer. Metabolically healthy men with obesity had a 67% increased risk of kidney cancer, and a 42% increased risk of colon cancer, but the relationship with both pancreatic cancer and rectal cancer was no longer statistically significant. In an unusual finding, both metabolically healthy and unhealthy men with overweight (not obesity) had around a 50% increased risk of the blood cancer multiple myeloma—yet neither metabolically healthy or unhealthy men with obesity had an increased risk of this cancer.

The authors said that, among men only, the data suggest that obesity jointly with metabolic complications increases the risk of these obesity-related cancers more than expected from the sum of either risk factor individually: "This has important public health implications, suggesting that a significant number of cancer cases could potentially be prevented by targeting the co-existence of metabolic problems and obesity, in particular for obesity-related cancers among men."

"This study highlights that the type of metabolic obesity phenotype is important when assessing obesity-related cancer risk,” the authors concluded. “In general, being metabolically unhealthy further increased the obesity-related cancer risk, suggesting that both obesity and metabolic conditions are useful targets for prevention for obesity-related cancers."


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