Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.

Chronic hepatitis B virus (HBV) infection is a challenging global health problem. To identify genetic loci involved in chronic HBV infection, we designed a three-phase genome-wide association study in Han Chinese populations. The discovery phase included 951 HBV carriers (cases) and 937 individuals who had naturally cleared HBV infection (controls) and was followed by independent replications with a total of 2,248 cases and 3,051 controls and additional replications with 1,982 HBV carriers and 2,622 controls from the general population. We identified two new loci associated with chronic HBV infection: rs3130542 at 6p21.33 (near HLA-C, odds ratio (OR) = 1.33, P = 9.49 × 10(-14)) and rs4821116 at 22q11.21 (in UBE2L3, OR = 0.82, P = 1.71 × 10(-12)). Additionally, we replicated the previously identified associations of HLA-DP and HLA-DQ variants at 6p21.32 with chronic HBV infection. These findings highlight the importance of HLA-C and UBE2L3 in the clearance of HBV infection in addition to HLA-DP and HLA-DQ.

Background: The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations.

Non-small-cell lung cancer (NSCLC) is one of the deadliest cancers in the world. Circular RNA (circRNA) has been shown to participate in oncogenesis regulation, including lung cancer. Although the involvement of circRNAs in lung cancer has been reported, the regulatory mechanisms of circRNAs in NSCLC remain poorly understood. Thus, the present study aims at investigating the role of circARHGAP10 in NSCLC progression, which has been observed to be significantly upregulated in both NSCLC tissues and cell lines with profile analysis. A higher expression of circARHGAP10 also leads to a poor prognosis in NSCLC patients with fluorescence in situ hybridization (FISH). Both in vitro and in vivo experiments found that the downregulation of circARHGAP10 suppressed glycometabolism by decreasing GLUT1 expression. Silencing cir-cARHGAP10 also suppressed proliferation and metastasis by targeting the miR-150-5p/GLUT1 axis in NSCLC, which was confirmed with a luciferase reporter assay. Overexpression of GLUT1 or downregulation miR-150-5p will recover NSCLC cell proliferation and metastasis after a knockdown of cir-cARHGAP10. Taken together, these findings demonstrate that circARHGAP10 suppresses NSCLC progression by acting as a miR-150-5p sponge to promote GLUT1 expression. Thus, circARHGAP10 may be a potential target for NSCLC treatment.