Objective: To explore the interaction between inheritance and environment with the aid of research on the genetic modes of hepatocellular carcinoma (HCC).
Methods: A genetic epidemiological study of HCC was conducted based on the methods of Penrose, simple segregation and Falconer for 100 proband pedigrees from HBsAg positive cohort. The proband samples came from a cohort of 90,00 people who were followed for 8 years. Analyses on genetic modes were carried out and heritability was calculated through the comparison of the proband pedigrees incidence frequency with incidence frequencies of the cohort and general population.
Results: The incidence frequency of first-degree relatives was 4.0%, higher than what was seen in the general population incidence frequency (0.44%) and the cohort (1.03%). A familial aggregation of HBsAg carriers and a strong positive correlation between HBsAg carrier status and HCC were noticed (OR = 8.44, 95% CI: 3.37-20.06, P < 0.001). A ratio of the incidence frequency among siblings to the incident frequency among general population (s/q) approached 1/q(1/2) by Penrose method, but simple segregation did not show agreement with single-gene inheritance. The heritability from positive cohort was 42% +/- 6% (P < 0.05), compared with the heritability (59% +/- 7%) of general population. When the effect of the HBsAg was under control, the heritability from positive cohort turned to be 29% +/- 8% (P < 0.05), compared with the heritability (47% +/- 7%) of general population.
Conclusion: Our findings suggested that HCC followed a multifactorial mode rather than single inheritance. An interaction effect of inheritance and environment on HCC was also noticed.