Socioeconomic inequalities, phenotypic aging, and the risk of incident upper gastrointestinal cancers

Although socioeconomic status (SES) and accelerated biological aging are considered to be linked with upper gastrointestinal cancers (UGICs) risk, there is limited longitudinal epidemiologic evidence elucidating their individual, combined effects, as well as potential intrinsic connections. Among 315,380 UGICs-free UK Biobank participants at baseline, latent class analysis was adopted to identify distinct SES groups, and biological aging was quantified by Phenotypic age acceleration (PhenoAgeAccel). We assessed the associations of SES and PhenoAgeAccel with incident UGICs, using multivariable Cox proportional hazards regression models, interaction and mediation analysis. There were 1,289 incident UGICs cases over a median follow-up of 12.5 years. Compared with high SES or biologically younger individuals, low SES (HR: 1.74; 95% CI: 1.42–2.14) or biologically older (HR: 1.66; 95% CI: 1.41–1.97) increased the risk of UGICs, respectively. There was a synergetic association of SES and PhenoAgeAccel with UGICs incidence, even though no significant additive and multiplicative interactions were detected. Moreover, PhenoAgeAccel acted as an effect modifier of the relationship between SES and UGICs, with mediating effects of 7.94%. In addition, a greater 5-year absolute risk reduction of UGICs (21.00 per 10,000 person years) was found in individuals with higher PhenoAgeAccel, especially for those at low SES. Lower SES and PhenoAgeAccel were independently and jointly associated with increased risk of UGICs. PhenoAgeAccel partially mediated the association of SES with UGICs.