#5 Birth cohort effect and the incidence of hepatocellular carcinoma

PURPOSE: The incidence of hepatocellular carcinoma (HCC) is rising in the US. Since HCC typically affects older people, this increase could have resulted from a shift in the population distribution to older age groups (age-effect). Alternatively, this could be due to an environmental exposure among successive cohorts (birth-cohort or period-effect). We conducted a study to disentangle these factors. METHODS: Using data from the SEER program, 5-year birth-cohorts were constructed for cases ages 20 and older diagnosed with HCC between 1974–98. HCC incidence was plotted as a function of 5-year age groups for each 5-year birth-cohort. Poisson regression analysis was used to quantify the significance of age and birth-cohort on the incidence of HCC. RESULTS: Between 1974–98, 11,710 individuals were diagnosed with HCC who were born between 1885–1974. A progressive increase in HCC incidence was observed for ages 45 years and older; however, a significant shift of cases toward younger age groups was seen in 1994–98 compared to 1974–78. In the birth-cohort analyses, older age group curves were generally higher than those of younger age groups (age-effect). However, most age curves were pointing upwards in the direction of more recent birth-cohorts, suggesting a birth-cohort effect. The absence of leveling off in most age curves indicated the lack of a period-effect. This birth-cohort effect was most evident for those born between 1910–1934. Results from the Poisson regression analysis confirmed age at diagnosis and birth-cohort to be independent predictors of HCC incidence. More recent birth-cohorts had a higher incidence of HCC, regardless of age group. The odds of developing HCC increased by 3% for each successive more recent 5-year birth-cohort, and 9% for each 5-year increase in age at diagnosis. CONCLUSION: A progressive shift towards younger age groups has accompanied the increase in HCC. Cohorts born after 1910 are at higher risk, irrespective of age, than those born earlier. Environmental exposures acquired at a younger age (e.g., Hepatitis C) could explain these findings.