Numerous studies have shown that aberrant microRNA (miRNA) expression is associated with the development and progression of various types of human cancer and serum miRNAs are potential biomarkers. This study examined whether some commonly deregulated miRNAs in hepatocellular carcinoma (HCC) are presented in serum of patients with HCC and can serve as diagnostic markers. Serum miRNAs (miR-21, miR-122, and miR-223) were quantified by real-time quantitative RT-PCR in 101 patients with HCC and 89 healthy controls. In addition, 48 patients with chronic type B hepatitis were also analyzed for comparison. We found that the median levels of miR-21, miR-122, and miR-223 were significantly higher in patients with HCC than those in healthy controls (P = 7.48 x 10⁻¹³, P = 6.93 x 10⁻⁹, and P = 3.90 x 10⁻¹², respectively). However, these elevated serum miRNAs were also detected in patients with chronic hepatitis (P = 2.05 x 10⁻¹², P = 4.52 x 10⁻¹⁶, and P = 1.65 x 10⁻¹¹, respectively). Moreover, serum miR-21 and miR-122 in patients with chronic hepatitis were higher than in patients with HCC (P = 3.99 x  10⁻⁴ and P = 4.97 x 10⁻⁸), although no such significant difference was found for miR-223. Receiver-operator characteristic (ROC) curve analyses suggest that these serum miRNAs may be useful markers for discriminating patients with HCC or chronic hepatitis from healthy controls, but not patients with HCC from patients with chronic hepatitis. Our results indicate that serum miR-21, miR-122 and miR-223 are elevated in patients with HCC or chronic hepatitis and these miRNAs have strong potential to serve as novel biomarkers for liver injury but not specifically for HCC.

Background: Recent genome-wide association studies have identified 10 single nucleotide polymorphisms (SNP) associated with colorectal cancer (CRC) in Caucasians. This study evaluated the effects of these newly identified SNPs in a Chinese population.Methods: We assessed the associations of these 10 SNPs with CRC in a case-control study that consisted of 2,124 cases and 2,124 controls. Odds ratios (OR) and 95% confidence intervals were computed by logistic regression, and cumulative effect of risk genotypes were also calculated.Results: We found that only five SNPs (rs6983267, rs4939827, rs10795668, rs3802842, and rs961253) were significantly associated with risk of CRC in our study population in the same direction as reported by previous genome-wide association studies, with the ORs ranging from 1.11 to 2.96. A cumulative effect was observed with the ORs being gradually elevated with increasing number of risk genotypes (P trend = 1.32 × 10 −21 ), and patients carrying ≥4 risk genotypes had 3.25-fold increased CRC risk (95% confidence interval,

APOBEC3s are a family of cytidine deaminases involved in innate cellular immunity against virus including hepatitis B virus (HBV). A germline deletion across APOBEC3A and APOBEC3B (A3B) genes results in complete removal of the A3B coding region and destroys A3B expression. To determine whether this deletion affects susceptibility to HBV infection and HBV-related hepatocellular carcinoma (HCC), A3B genotypes were analyzed in 1124 individuals with HCC, 510 individuals with persistent HBV infection and 826 healthy controls and the association was estimated by odds ratio (OR) and 95% confidence interval (CI) computed by logistic regression. We also examined the effects of A3B on HBV genome hypermutation and replication in HCC cells. We observed a significantly higher frequency of the A3B deletion allele in persistent HBV carriers (33.3%; P = 0.0015) and HCC patients (37.9%; P = 1.28 × 10(-11)) compared with that in controls (27.5%). An increased risk for persistent HBV infection (OR = 1.35, 95% CI: 1.03-1.77) and HCC development (OR = 1.90, 95% CI: 1.58-2.28) was associated with at least one A3B deletion allele (+/- or -/- genotype) compared with the +/+ genotype. Transfection of A3B in HepG2 cells caused a substantial reduction of HBV RNA levels and G → A hypermutation in the HBV genome. Interestingly, a cytidine deaminase null mutant of A3B (E255A) also inhibited HBV RNA production although it was unable to edit HBV. These results suggest that the deletion of A3B attenuates HBV clearance, which in turn may result in persistent HBV infection and increased risk for developing HCC. Further studies are needed to verify our findings.

Although most patients with small-cell lung cancer respond to chemotherapy, the survival time is highly diverse. We conducted a genome-wide analysis to examine whether germline genetic variations are prognostic factors in small-cell lung cancer patients treated with the same chemotherapy regimen. Genome-wide scan of single nucleotide polymorphisms (SNP) was performed using blood DNA to identify genotypes associated with overall survival in 245 patients treated with platinum-based chemotherapy, and the results were replicated in another independent set of 305 patients. Associations were estimated by Cox models and function of the variants was examined by biochemical assays. We found that rs1820453 T>G SNP within the promoter region of YAP1 on chromosome 11q22 and rs716274 A>G SNP in the region of downstream of DYNC2H1 on chromosome 11q22.3 are associated with small-cell lung cancer survival. In pooled analysis of 2 independent cohorts, the adjusted hazard ratio for patients with the rs1820453 TG or GG genotype was 1.49 (95% CI, 1.19-1.85; P ¼ 0.0004) and 1.65 (95% CI, 1.36-2.01; P ¼ 4.76 Â 10 À7 ), respectively, compared with the TT genotype; and for patients with the rs716274 AG or GG genotype was 1.83 (95% CI, 1.47-2.29; P ¼ 8.74 Â 10 À8 ) and 2.96 (95% CI, 1.90-4.62; P ¼ 1.59 Â 10 À6 ), respectively, compared with the AA genotype. Functional analysis showed that the rs1820453 T>G change creates a transcriptional factor binding site and results in downregulation of YAP1 expression. These results suggest that YAP1 may play an important role in prognosis of small-cell lung cancer patients treated with platinum-based chemotherapy. Cancer Res; 70(23); 9721-9. Ó2010 AACR.