Estrogen receptor alpha polymorphisms associated with susceptibility to hepatocellular carcinoma in hepatitis B virus carriers.
OBJECTIVE
Overexpression of estrogen receptors (ESRs) is implicated in the development of hepatocellular carcinoma (HCC) in both animal models and humans. We examined whether the ESR1 polymorphisms were related to HCC risk among chronic hepatitis B virus carriers.


METHODS
Six ESR1 polymorphisms, which are (TA)n repeat in the promoter, T29C at codon 10 in exon 1, PvuII and XbaI site in intron 1, C136474G at codon 325 in exon 4, and A252966G in intron 5, were genotyped in 248 patients with HCC and 239 controls. The associations with the susceptibility to HCC were estimated by logistic regression. Allele-specific transcription difference of ESR1 messenger RNA was performed by real-time quantitative polymerase chain reaction.


RESULTS
We observed a statistically significant increased susceptibility to HCC associated with the homozygous alleles with a high number of TA repeats (assigned as H/H genotype; odds ratio [OR], 2.66; 95% confidence interval [CI], 1.44-4.94; P = .0018), T29C C/C genotype (OR, 2.31; 95% CI, 1.25-4.26; P = .0076), and PvuII C/C genotype (OR, 2.19; 95% CI, 1.27-3.78; P = .0048) compared with the homozygous alleles with a low number of TA repeats (assigned as L/L genotype), T29C T/T, and PvuII T/T genotype, respectively. In accordance, the relative messenger RNA levels of the at-risk C allele of T29C were consistently higher than those of the T allele in heterozygous cells.


CONCLUSIONS
Our findings suggest that the genetic polymorphism in ESR1 may play a role in mediating susceptibility to HCC in Chinese hepatitis B virus carriers.
Zhai
Yun
Y
Department of Genomics & Proteomics, Beijing Institute of Radiation Medicine, Beijing, China.
Zhou
Gangqiao
G
Deng
Guohong
G
Xie
Weimin
W
Dong
Xiaojia
X
Zhang
Xiumei
X
Yu
Ling
L
Yang
Hao
H
Yuan
Xiaoyan
X
Zhang
Hongxin
H
Zhi
Lianteng
L
Yao
Zhijian
Z
Shen
Yan
Y
Qiang
Boqing
B
He
Fuchu
F
D000328:Adult; D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D004279:DNA, Viral / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015995:Prevalence; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment
D004279:DNA, Viral; D047628:Estrogen Receptor alpha