title: Dominance of functional androgen receptor allele with longer CAG repeat in hepatitis B virus-related female hepatocarcinogenesis.
abstract: The CAG polymorphism in exon 1 of the androgen receptor (AR) gene has been shown associated with the development of human male hepatocellular carcinoma (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.
authors.affiliation: Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shiou-Hwei
authors.initials: SH
authors.lastname: Yeh
authors.forename: Ching-Fung
authors.initials: CF
authors.lastname: Chang
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Shau
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Hey-Chi
authors.initials: HC
authors.lastname: Hsu
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D022981:Allelic Imbalance; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D019175:DNA Methylation; D005260:Female; D006509:Hepatitis B / Q000150:complications* / Q000235:genetics; D006515:Hepatitis B virus; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008875:Middle Aged; D011944:Receptors, Androgen / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D011944:Receptors, Androgen