10 research outputs found

    Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”

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    We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs—PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616—were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-allele<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. Pper-allele≥0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele = 0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04–1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus

    EXTRACTION OF THE GLUON DENSITY OF THE PROTON AT X RID B-9165-2008 RID C-5889-2009 RID A-4818-2008 RID C-1693-2008

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    The gluon momentum density xg(x, Q(2)) of the proton was extracted at Q(2) = 20 GeV2 for small values of x between 4 x 10(-4) and 10(-2) from the scaling violations of the proton structure function F-2 measured recently by ZEUS in deep inelastic neutral current ep scattering at HERA. The extraction was performed in two ways. Firstly, using a global NLO fit to the ZEUS data on F-2 at low x constrained by measurements from NMC at larger x; and secondly using published approximate methods for the solution of the GLAP QCD evolution equations. Consistent results are obtained. A substantial increase of the gluon density is found at small x in comparison with the NMC result obtained at larger values of x

    Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences

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