Androgen receptor exon 1 CAG repeat length and risk of hepatocellular carcinoma in women

Hepatology. 2002 Jul;36(1):156-63. doi: 10.1053/jhep.2002.33897.

Abstract

The androgen receptor (AR) gene is localized on chromosome X, and shorter CAG repeats in exon 1 of the AR gene were recently suggested to increase hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk among men. To examine whether the relationship between the AR-CAG repeats and HCC was also evident among women, we conducted a case-control study in Taiwan. The number of AR-CAG repeats was determined for 238 women with HCC and 354 unrelated control subjects (comprising 188 first-degree and 166 nonbiological relatives) selected from female relatives of patients with HCC. Women harboring 2 AR alleles with more than 23 CAG repeats had an increased risk of HCC (age-adjusted odds ratio [OR], 1.82; 95% CI, 1.06-3.14), compared with women with only short alleles or a single long allele. The association between harboring 2 AR alleles containing longer CAG repeats and HCC was more striking among HBV carriers (age-adjusted OR for more than 22 repeats, 2.23; 95% CI, 1.14-4.34) and particularly prominent among HBV carriers under age 53 years (age-adjusted OR, 3.16; 95% CI, 1.13-8.82). When CAG repeats were analyzed as a continuous variable, the increase in HCC risk associated with each incremental repeat in the shorter of 2 alleles in a given genotype was statistically significant among women with a first-degree relative with HCC (age-adjusted OR, 1.18; 95% CI, 1.01-1.37). No such relationship was detected among women without the family history. In conclusion, our observations suggest that the AR-CAG alleles may contribute to HCC predisposition among women through a mechanism different from that for men.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Carcinoma, Hepatocellular / genetics*
  • Exons*
  • Female
  • Genetic Predisposition to Disease*
  • Hepatitis B Surface Antigens / blood
  • Heterozygote
  • Homozygote
  • Humans
  • Liver Neoplasms / genetics*
  • Middle Aged
  • Odds Ratio
  • Receptors, Androgen / genetics*
  • Risk Factors
  • Taiwan
  • Trinucleotide Repeats*

Substances

  • Hepatitis B Surface Antigens
  • Receptors, Androgen