AbstractBackgroundUS‐born Latinos have a higher incidence of hepatocellular carcinoma (HCC) than foreign‐born Latinos. Acculturation to unhealthy lifestyle behaviors and an immigrant self‐selection effect may play a role. In this study, the authors examined the influence of generational status on HCC risk among Mexican American adults.MethodsThe analytic cohort included 31,377 self‐reported Mexican Americans from the Multiethnic Cohort Study (MEC). Generational status was categorized as: first‐generation (Mexico‐born; n = 13,382), second‐generation (US‐born with one or two parents born in Mexico; n = 13,081), or third‐generation (US‐born with both parents born in the United States; n = 4914). Multivariable Cox proportional hazards regression was performed to examine the association between generational status and HCC incidence.ResultsIn total, 213 incident HCC cases were identified during an average follow‐up of 19.5 years. After adjusting for lifestyle and neighborhood‐level risk factors, second‐generation and third‐generation Mexican Americans had a 37% (hazard ratio [HR], 1.37; 95% confidence interval [CI], 0.98–1.92) and 66% (HR, 1.66; 95% CI, 1.11–2.49) increased risk of HCC, respectively, compared with first‐generation Mexican Americans (p for trend = 0.012). The increased risk associated with generational status was mainly observed in males (second‐generation vs. first‐generation: HR, 1.60 [95% CI, 1.05–2.44]; third‐generation vs. first‐generation: HR, 2.08 [95% CI, 1.29–3.37]).ConclusionsIncreasing generational status of Mexican Americans is associated with a higher risk of HCC. Further studies are needed to identify factors that contribute to this increased risk.