Segregation analysis of hepatocellular carcinoma in a moderately high-incidence area of East China.

AIM: To explore the mode of inheritance of hepatocellular carcinoma (HCC) in a moderately high-incidence area of East China. METHODS: A pedigree survey was conducted in 210 families (3315 individuals) ascertained through 210 HCC probands in Haimen, Jiangsu Province. Simple segregation analysis was conducted using SEGRANB software. The probability of ascertainment (pi), segregation ratio (p), and the proportion of sporadic cases (x) were estimated. Complex segregation analysis was performed using the REGTL program of S.A.G.E. Models were fitted on the data of 3212 individuals that allowed for personal HBsAg status and variable age of onset in REGTL program. RESULTS: The estimate of segregation ratio was 0.191 by SEGRANB. The probability of ascertainment was 0.0266, and the proportion of sporadic cases was 0.465. The results of complex segregation analysis showed that Mendelian autosomal recessive inheritance of a major gene that influenced the age of onset distribution of HCC, provided the best fit to the data. In the best-fitting recessive model, the frequency of the disease allele was 0.11138. HBsAg seropositive status would significantly increase the risk of developing HCC. CONCLUSION: These results suggest that at least one major gene is involved in the genetic predisposition to develop HCC at an earlier age of onset. The seropositive HBsAg status can significantly increase the risk of developing HCC, which provides strong support for the interaction between genetic and environmental risk factors.

[A study on the relationship of birth order hepatocellular carcinoma].

OBJECTIVE: To explore the association of hepatocellular carcinoma (HCC) with environmental factors through analyzing birth order data from pedigree sibships. METHODS: A birth order study was conducted based on the methods of Greenwood and Haldane for 100 probands and 22 affected siblings from 100 pedigrees in a cohort which was followed up for 8 years in Haimen, Jiangsu, China. RESULTS: The findings from the Greenwood method suggested that there was a tendency for cases of HCC to concentrate at lower birth orders of 1 to 3. With the effects of hepatitis B virus on the birth orders being controlled, the same tendency was also observed. The results from Haldane method showed that difference between actual value and expected value of 6A was more than the double standard deviation. Sigma 6A(actual value) = 1,806, Sigma 6A(expected value) = 1,988, the absolute value of (Sigma 6A(actual value) - Sigma 6A(expected value))/the square root of Sigma V6A = 2.1657 (0.02 < P < 0.05). The actual value of 6A was lower than the expected value of 6A suggesting that individuals at lower birth orders were at a higher risk of suffering from HCC. In addition, through data from ecologic research, there was a decreasing tendency of mortality of HCC within 10 years after the prevalence of tap water in Haimen city. The correlation coefficient by Spearman test was -0.818 (P < 0.01). The contribution of the quality of drinking water in the locality to the onset of HCC was found among people born in earlier period. CONCLUSIONS: There was a tendency that the onset of HCC cases concentrating was at lower birth orders in this research, which was inconsistent with several reports of foreign authors' which showed a reverse tendency. According to the ecological results, it was suggested that long-term drinking of ditch-water was responsible for the tendency of cases of HCC concentrating at lower birth orders. There were also certain effects of environmental factors exerted on the onset of HCC being discovered.