Our data in surgically resected human HCC and a mouse model of find more carcinogen-induced HCC support a potential tumor suppressor function of Col18a1. Further studies are underway to establish what roles Col18a1 may play in controlling the rates of HCC progression. Disclosures: Lewis R. Roberts – Grant/Research Support: Bristol Myers Squibb, ARIAD Pharmaceuticals, BTG, Wako Diagnostics, Inova Diagnostics, Gilead Sciences The following people have nothing to disclose: Michael Duncan, Renumathy Dhanasekaran, Priyanka Thakur Background & Aims: Recent single nucleotide polymorphism (SNP) studies revealed several host genetic risk factors for hepatocellular carcinoma (HCC); however, the majority
of genetic factors remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs that control
gene expression post-transcrip-tionally. As for HCC, two common SNPs in mature miRNAs (rs2910164 in miR-146a and rs11614913 in miR-196a2) have been extensively studied, but published results are inconsistent and inconclusive. Almost all these studies compared hepatitis B virus (HBV)-related HCC patients and healthy controls in China. We aimed to investigate the association between these Erlotinib SNPs and HBV-related as well as hepatitis C virus (HCV)-related HCC risk in a Japanese population using a large number of patients. Methods: We analyzed the effect of rs2910164 and rs11614913 on HCC development in over 1,500 chronic HBV patients, including 407 with HCC (cases) and 1,141 without HCC (controls), and over 3,300 chronic HCV patients, including 1,026 cases and 2,349 controls, by multiplex-PCR-based Invader assay. Results: According to 1000Genomes database, risk allele frequencies (AFs) of rs2910164 and of rs11614913 vary among ethnic groups: 0.22 and 0.41 in Europeans, 0.54 and 0.58 in Han Chinese, and 0.60 and 0.60 in Japanese, respectively. Estimated statistical power is 60% and over 90% for our HBV and HCV studies, respectively. First, we analyzed chronic HBV patients and found that risk AF of rs2910164 was significantly higher in cases than in controls (P = 0.040, odds ratio [OR] = 1.19).
We also found a similar result for rs11614913 (P = 0.017, OR = 1.21). Because both of age and male ratio were significantly higher in cases than controls, we adjusted for age and gender and again found significant associations with HBV-related HCC for both SNPs (P = 0.014 and 0.037, OR = 1.23 and 1.19, respectively). Next, we analyzed chronic HCV patients, but we could not find any significant differences between risk AFs of cases and those of controls for either SNP (P = 0.266 and 0.861, respectively), despite sufficient statistical power. After adjusting for age and gender, we again observed no association. Finally, we investigated the association between these two SNPs and expression of possible target genes using expression quantitative trait loci (eQTL) with public databases, but we failed to find any supporting evidence.