This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yeh, S.-H. Articles by Chen, P.-J. Search for Related Content PubMed PubMed Citation Articles by Yeh, S.-H. Articles by Chen, P.-J.

Dominance of Functional Androgen Receptor Allele with Longer CAG Repeat in Hepatitis B Virus-related Female Hepatocarcinogenesis¹

Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan [S-H. Y., C-F. C., Y-W. C., D-S. C., P-J. C.]; Division of Molecular and Genomic Medicine, National Health Research Institutes, Taipei 115 Taiwan [S-H. Y.]; and Graduate Institute of Clinical Medicine, Departments of Pathology [H-C. H.], Surgery [P-H. L.], and Internal Medicine College of Medicine [D-S. C.], National Taiwan University, Taipei 100, Taiwan

The CAG polymorphism in exon 1 of the androgen receptor (AR) gene has been shown associated with the development of human male hepatocellularcarcinoma (HCC) with the shorter AR alleles conferring a higher risk. However, the significance of AR-CAG repeats in female hepatocarcinogenesis remains to be addressed. In this study, seventy-six pairs of female HCCs and corresponding nontumorous tissues were collected, and 180 cirrhotic nodules were microdissected from 7 cirrhotic livers. The clonality status, functional AR alleles, and CAG repeat number of each sample were determined by AR methylation analysis. In a total of 44 monoclonal HCCs, the mean of CAG repeats in the active alleles was significantly longer than that in the inactive alleles (22.0 ± 2.8 versus 20.7 ± 3.6; P = 0.047). When we divided HCCs into hepatitis B virus-positive [HBV(+)] and HBV(-) subgroups, the long AR allele dominance was found only in HBV(+) ones (P = 0.006 versus P = 0.923). Notably, the preference of long CAG repeat has also been found in the 100 monoclonal nodules (P = 0.013). For comparison of monoclonal nodules obtained from the same individual, a dominant long AR allele was found in 6 patients. The proportion of monoclonal cirrhotic nodules and HCCs expressing longer AR allele, 69 and 68%, are both significantly higher than 50%, the assumed value in normal liver (P < 0.001 for cirrhotic nodules and P = 0.005 for HCC). The dominance is again only prominent in HBV-infected HCCs [85% for HBV(+) HCC; P < 0.001 but 54% for HBV(-) HCC; P = 0.27]. The results indicated that in female hepatocarcinogenesis, hepatocytes expressing the longer AR allele seem to be favorably selected for autonomous growth and transformation, especially in synergy with HBV infection.