Metabolically (un)healthy obesity and risk of obesity-related cancers: a pooled study

Abstract

Background Studies of obesity with or without metabolic aberrations, commonly termed metabolically unhealthy or healthy obesity, in relation to cancer risk are scarce. Methods We 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 mid-blood pressure, plasma glucose and triglycerides was used to define metabolically healthy and unhealthy status. Hazard ratios (HRs) and multiplicative interactions were assessed using Cox regression, and additive interactions were assessed using the relative excess risk for interaction. All statistical tests were two-sided. Results Metabolically unhealthy obesity, with a baseline prevalence of 7%, was, compared to metabolically healthy normal weight, associated with an increased relative risk of any obesity-related cancer and of colon, rectal, pancreas, endometrial, liver, gallbladder, and renal cell cancer (p < 0.05), with the highest risk estimates for endometrial, liver, and renal cell cancer (HRs, 2.55 to 3.00). Metabolically healthy obesity showed a higher relative risk for any obesity-related cancer and colon (in men), endometrial, renal cell, liver, and gallbladder cancer, though the risk relationships were weaker. There were no multiplicative interactions, but there were additive, positive interactions between BMI and metabolic health status on obesity-related and rectal cancer among men, and on endometrial cancer (p < 0.05). Conclusions This study highlights that the type of metabolic obesity phenotype is important when assessing obesity-related cancer risk. In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that both obesity and metabolic aberrations are useful targets for prevention.

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

“…). 35 This study concluded that metabolic dysfunction further increases ORC risk and may be a useful target for prevention in addition to obesity. Additionally, using UK Biobank data on 390,575 individuals, Cao et al 19 observed that MUO individuals had a higher risk of 10 ORCs, in contrast to MHO individuals that had a higher risk of only five ORCs.…”

“…Other reports have observed associations of cancer with the metabolically unhealthy phenotypes, either with 11–13,34 or independent from obesity 14–21 . A recent pooled analysis of 797,193 participants in the Metabolic syndrome and Cancer (Me‐Can) project 2.0 observed statistically significant higher risks of ORC with all abnormal metabolic obesity phenotypes, with metabolically unhealthy obese individuals having the greatest risk ([OR (95% CI): 1.91 (1.74–2.09) and 1.43 (1.35–1.51), in men and women, respectively]) 35 . This study concluded that metabolic dysfunction further increases ORC risk and may be a useful target for prevention in addition to obesity.…”

Adiposity and cancer: meta-analysis, mechanisms, and future perspectives

“…Approximately 10-30% of individuals with obesity maintain metabolic health characterised by an absence of conditions such as gallstones, diabetes, hyperinsulinemia, dyslipidaemia, or fatty liver 6 . These individuals may have lower cancer risks compared with their metabolically unhealthy counterparts, though risk remains higher than those who are metabolically healthy and lean 6,86 .…”

Epigenetic modifications in obesity‐associated diseases

“…A large proportion of cancer cases in many regions and countries can be attributed to obesity and overweight 5 . Compared with metabolically healthy individuals with normal weight, metabolically healthy obese individuals have an approximately 30% increased risk of obesity‐associated cancers, while the risk is even more significant for metabolically unhealthy obese individuals 6 . In America, obesity has gradually surpassed tobacco as the leading preventable cancer cause 7 .…”

“…5 Compared with metabolically healthy individuals with normal weight, metabolically healthy obese individuals have an approximately 30% increased risk of obesityassociated cancers, while the risk is even more significant for metabolically unhealthy obese individuals. 6 In America, obesity has gradually surpassed tobacco as the leading preventable cancer cause. 7 Prostate cancer (among males) and breast cancer (BC) (among females) have emerged as the leading types of cancer, surpassing lung cancer, as per the latest research data from the American Cancer Society.…”