Metabolic dysfunction and obesity‐related cancer: Results from the cross‐sectional National Health and Nutrition Examination Survey

Abstract

Background Metabolic syndrome (MetS), a group of risk factors that define metabolic dysfunction in adults, is strongly associated with obesity and is an emerging risk factor for cancer. However, the association of MetS and degree of metabolic dysfunction with obesity‐related cancer is unknown. Methods Using National Health and Nutrition Examination Survey data from 1999 to 2018, we identified 528 obesity‐related cancer cases and 18,972 cancer‐free participants. MetS was defined as the presence of or treatment for ≥3 of hyperglycemia, hypertension, hypertriglyceridemia, low HDL–cholesterol, and abdominal obesity. A metabolic syndrome score (MSS) was computed as the total number of abnormal MetS parameters to determine the severity of metabolic dysfunction. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression models, adjusting for sociodemographic and lifestyle factors. Results About 45.7% of obesity‐related cancer cases were classified as having MetS compared with only 33.0% of cancer‐free participants. Overall, MetS and MSS were not associated with obesity‐related cancer. However, MSS was associated with higher obesity‐related cancer risk among participants under 50 years of age (OR [95% CI] = 1.28 [1.08–1.52]). When evaluating MSS categorically, compared with healthy participants with no abnormal MetS parameters (MSS = 0), participants with one or two abnormal parameters had a statistically significant higher risk of obesity‐related cancer (OR [95% CI] = 1.73 [1.06–2.83]). Conclusions Metabolic dysfunction is associated with a higher risk of obesity‐related cancer, particularly in young adults under 50 years of age, and among participants with one or two abnormal metabolic parameters. A more accurate indicator of metabolic dysfunction, beyond metabolic syndrome, is needed to better assist in stratifying individuals for obesity‐related cancer risk.

Metabolically defined body size and body shape phenotypes and risk of postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition

“…Moreover, in several studies, similar results were reported when a single marker was used to define metabolic health compared with the use of MetS. 36 , 37 , 52 Another limitation of the study includes the small sample size in some subgroup analyses, and the incomplete information on breast cancer subtypes. The observed associations may vary according to breast cancer receptor subtype since a recent study reported a strong positive association between MUOW/OB phenotype and estrogen receptor‐positive breast cancer risk.…”

“…The authors suggest that being metabolically unhealthy as the presence of at least one, two, or three MetS criteria, regardless of BMI category, is associated with a higher risk of at least four cancer types. Moreover, in several studies, similar results were reported when a single marker was used to define metabolic health compared with the use of MetS 36,37,52 . Another limitation of the study includes the small sample size in some subgroup analyses, and the incomplete information on breast cancer subtypes.…”

Metabolic obesity phenotypes and obesity‐related cancer risk in the National Health and Nutrition Examination Survey

“…Although evidence supporting a relationship between metabolic dysfunction and cancer risk has been increasing, 27–29 the mechanisms are still poorly understood. The most commonly hypothesized mechanism is chronic inflammation resulting from excess adipose tissue, including immune cell infiltration, and cytokine and chemokine release that creates a preneoplastic microenvironment 4,30,31 .…”