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


CONCLUSIONS
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.
Cai
Ru-Lin
RL
Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032, China. wmeng@shmu.edu.cn
Meng
Wei
W
Lu
Hong-Yan
HY
Lin
Wen-Yao
WY
Jiang
Feng
F
Shen
Fu-Min
FM
D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000235:genetics*; D002681:China / Q000453:epidemiology; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011336:Probability; D012984:Software