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

Hepatocellular carcinoma (HCC) is an epithelial cancer which originates from hepatocytes or their progenitors As a positive regulator Of NF kappa B signaling pathway, beta-transducin repeat-containing protein (beta TrCP) is overexpressed and oncogenic in epithelial cancers, suggesting a potential role of beta TrCP 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 9 bp insertion/deletion polymorphism (rs16405) in 3' untranslated region of beta TrCP. 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 beta TrCP from HCC tumor tissues were correlated with rs16405 genotypes. HCC tumor tissues with homozygous for 9N ins/ins has the highest level of beta TrCP, 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 rs 16405 disrupted a binding site for human microRNA-920 which would negatively regulate beta TrCP We propose a microRNA-920 mediated beta TrCP regulation model depending on rs 16405 genotype, which warrants further replication association studies and foilow-up functional experiments (C) 2009 Elsevier Inc All rights reserved.