Colorectal cancer (CRC) remains a leading global cancer burden. Concurrent increases in metabolic syndrome (MetS) prevalence and changing CRC age distribution have prompted investigation of whether MetS-related cancer risk varies by age and sex. Prior studies report associations between MetS and CRC overall and have suggested heightened risk in younger populations, but few studies jointly stratify by age and sex to characterise heterogeneity in risk. The present analysis used UK Biobank data to define age- and sex-specific associations between MetS and incident CRC and to inform targeted prevention strategies.
This study drew on the UK Biobank, a large population-based prospective cohort that recruited over 500,000 adults aged 40–69 years between 2006 and 2010 from 22 assessment centres across England, Scotland, and Wales. For the present analysis, individuals with a previous cancer diagnosis (except non-melanoma skin cancer) or with missing data on MetS components were excluded. The final analytic sample comprised 379,173 participants. Median follow-up for cancer outcomes was 11.8 years, during which 4,971 incident CRC cases occurred.
MetS was operationalised according to widely used harmonised criteria requiring the presence of at least three of five metabolic abnormalities. The five components were:
Glycaemic status used HbA1c rather than fasting glucose because UK Biobank measurements were non-fasting.
Incident CRC cases were identified through linkage to national cancer registries and hospital records using ICD-10 codes C18–C20. Registry coverage varied by nation with censoring dates reported for England, Wales, and Scotland; hospital episode statistics were used to capture cases beyond registry cutoffs where available. Follow-up extended through registry and hospital data sources as specified in the study.
Baseline assessments provided demographic, socioeconomic, lifestyle, diet, screening, family history, and medication data. Key covariates included age, self-reported ethnicity (White, Other), Townsend deprivation index, education level, smoking status, alcohol consumption frequency, physical activity (IPAQ categories), fruit and vegetable intake, red/processed meat intake, CRC screening history, family history of CRC in first-degree relatives, and regular NSAID/aspirin use.
The authors used multivariable Cox proportional hazards models to estimate associations of MetS, the number of metabolic abnormalities, and each MetS component with incident CRC. Participants were stratified jointly by sex and age (<60 vs ≥60 years) into four groups to examine effect heterogeneity. Models adjusted for a comprehensive set of demographic, lifestyle, dietary, medical, and socioeconomic covariates. Early-onset CRC (diagnosed before 50) was noted to be too infrequent in this cohort for meaningful separate analysis.
Among 379,173 participants, 4,971 developed CRC during median 11.8 years’ follow-up. The principal exposure, MetS, and its individual components were evaluated for associations with CRC overall and within the four age–sex strata.
Key reported hazard ratios (HRs) for MetS and CRC were:
These findings indicate that the MetS–CRC association is dependent on both age and sex, with young and middle-aged males showing the highest relative risk in this White UK Biobank population.
When examining individual components, elevated waist circumference emerged as the only MetS component consistently associated with higher CRC risk in all groups except younger females, per the reported results. Additionally, among older males but not older females, there was an observed dose–response pattern: having 3, 4, or 5 metabolic abnormalities was associated with progressively higher CRC risk compared with having none.
The study concludes that the relationship between metabolic syndrome and colorectal cancer is modified by both age and sex in the study population, with the greatest excess risk concentrated in younger males. Elevated waist circumference appears to be a key driver of the observed associations. The authors suggest these results support risk-stratified prevention efforts and motivate further research into sex- and age-specific biological mechanisms underlying MetS-associated colorectal carcinogenesis.
Strengths include the large prospective cohort design, standardized baseline assessments, comprehensive covariate data, and long median follow-up with linkage to cancer registries and hospital records. Limitations noted in the source include the inability to meaningfully analyse early-onset CRC separately due to small numbers within the cohort and that findings reflect the demographic composition of the UK Biobank (predominantly White participants), which may limit generalisability to other populations. Specific additional limitations or sensitivity analyses were not detailed in the provided source excerpt.