Association of Lifestyle Behaviors and Cancer Risk in MetALD

Background: Metabolic and alcohol-associated liver disease (MetALD) has been associated with an increased risk of cancer. However, it remains unclear whether combinations of favorable, intermediate, and adverse lifestyle behaviors differentiate cancer risk within MetALD. Methods: We analyzed 25,712 participants with MetALD using UK Biobank. Smoking, moderate-to-vigorous physical activity (MVPA), and diet were classified into favorable, intermediate, and adverse categories. Favorable and adverse behavior counts ranged from 0 to 3, and a unified lifestyle profile was constructed. Cox proportional hazards models were used to analyze adjusted hazard ratios (aHRs) and 95% confidence interval (CI) for incidence of all cancers. Results: During 296,965 person-years of follow-up, 4416 incident cancers occurred. Compared with no favorable behaviors, those having two favorable behaviors showed significance 0.92 (95% CI, 0.84-1.00). Compared with no adverse behaviors, the aHRs were 1.06 (95% CI, 1.00-1.13), 1.15 (95% CI, 1.04-1.27), and 1.11 (95% CI, 0.84-1.47) for one, two, and three adverse behaviors, respectively (p for trend = 0.003). The mixed/intermediate profile was associated with higher cancer risk than the favorable profile (aHR, 1.09; 95% CI, 1.02-1.16), whereas the adverse-profile estimate was not statistically significant. Among individual lifestyle behaviors, current smoking was associated with a higher cancer risk than never smoking (aHR, 1.20; 95% CI, 1.09-1.32; p < 0.001). Conclusions: Among participants with MetALD, favorable and adverse behavior counts showed opposite adjusted trends in cancer risk. Current smoking showed the strongest association with cancer risk among the individual behaviors.