Androgen receptor exon 1 CAG repeat length and risk of hepatocellular carcinoma in women.
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.
Yu
Ming-Whei
MW
Department of Public Health and Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, No. 1 Jen-Ai Road, Section 1, Room 1550, Taipei 100, Taiwan. mingwhei@ha.mc.ntu.edu.tw
Yang
Yu-Ching
YC
Yang
Shi-Yi
SY
Chang
Hung-Chuen
HC
Liaw
Yun-Fan
YF
Lin
Shi-Ming
SM
Liu
Chun-Jen
CJ
Lee
Shou-Dong
SD
Lin
Chih-Lin
CL
Chen
Pei-Jer
PJ
Lin
Shee-Chan
SC
Chen
Chien-Jen
CJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D011944:Receptors, Androgen / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan; D018911:Trinucleotide Repeats
D006514:Hepatitis B Surface Antigens; D011944:Receptors, Androgen