An insertion/deletion polymorphism in the 3' untranslated region of beta-transducin repeat-containing protein (betaTrCP) is associated with susceptibility for hepatocellular carcinoma in Chinese

Biochemical and Biophysical Research Communications
Shougong ChenYuzhen Gao

Abstract

Hepatocellular carcinoma (HCC) is an epithelial cancer which originates from hepatocytes or their progenitors. As a positive regulator of NFkappaB signaling pathway, beta-transducin repeat-containing protein (betaTrCP) is overexpressed and oncogenic in epithelial cancers, suggesting a potential role of betaTrCP in HCC susceptibility. We carried out a case-control study in a Chinese population (256 cases and 367 controls) to estimate the susceptibility to HCC associated with a 9bp insertion/deletion polymorphism (rs16405) in 3' untranslated region of betaTrCP. Using unconditional logistic regression, we found that 9N del/del and 9N ins/del genotypes were significantly associated with decreased HCC risk: OR=0.44 (0.24-0.83) (p=0.004) and OR=0.56 (0.31-1.00) (p=0.034), respectively. Furthermore, in vivo experiments showed that mRNA levels of betaTrCP from HCC tumor tissues were correlated with rs16405 genotypes. HCC tumor tissues with homozygous for 9N ins/ins has the highest level of betaTrCP, which are 3.99 and 7.04-fold higher than heterozygous 9N ins/del and homozygous 9N del/del, respectively. Based on bioinformatics prediction, we found that the risk allele for rs16405 disrupted a binding site for human microRNA-920 which wo...Continue Reading

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