59 research outputs found

    Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

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    We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies

    Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

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    Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology

    Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

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    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene

    Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

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    We performed a multistage genome-wide association study (GWAS) including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT; per-allele odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.74–0.84; P = 3.0×10−12), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2; OR = 1.46; 95% CI = 1.30–1.65; P = 1.1×10−10), rs9581943 at 13q12.2 (PDX1; OR = 1.15; 95% CI = 1.10–1.20; P = 2.4×10−9), and rs16986825 at 22q12.1 (ZNRF3; OR = 1.18; 95% CI = 1.12–1.25; P = 1.2×10−8). An independent signal was identified in exon 2 of TERT at the established region 5p15.33 (rs2736098; OR = 0.80; 95% CI = 0.76–0.85; P = 9.8×10−14). We also identified a locus at 8q24.21 (rs1561927; P = 1.3×10−7) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study has identified multiple new susceptibility alleles for pancreatic cancer worthy of follow-up studies

    A Preliminary ecotoxicological assessment of Asian carp species in the Mississippi and Illinois Rivers

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    Project Completion Report issued March 2005Report issued on: March 2005INHS Technical Report prepared for Illinois - Indiana Sea Gran

    Interface-driven phase-separated coatings

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    A homogeneous mixture of two polymers dissolved in a common solvent or a mixture of solvents was applied as a thin film. The first component was a bisphenol-A based epoxide derivative modified with tetraethoxysilane (TEOS) oligomer and the second component was a high-solids fluorinated acrylic copolymer. The thin films were coated on steel substrates and were thermally crosslinked using a methylated melamine formaldehyde and/or a polyamide-amine curing agent. The films were evaluated via x-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) with integrated energy dispersive spectroscopy (EDS). It was found that the molecular weight of the resins, fluorine content, epoxide inorganic modification, and curing agent affected the degree of stratification

    Modified Soybean Oil-Extended SBR Compounds and Vulcanizates Filled with Carbon Black

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    Soybean oil (SO) was modified through the reaction with dicyclopentadiene (DCPD) to convert carbon double bonds in the soybean oil molecules into norbornyl groups of different ratios. Styrene-butadiene rubber (SBR) compounds with carbon black (CB) containing different extender oils including SO, modified SO (MSO) and naphthenic oil (NO) were prepared for comparison. The gel fraction, crosslink density, bound rubber fraction, curing behavior, thermal, mechanical and dynamic properties and reactions between the SO, MSO and curatives were investigated. It was found that with an increase of the modification level, the gel fraction of the SBR/MSO vulcanizates slightly increased while the crosslink density and bound rubber fraction decreased. The SBR/SO and SBR/MSO compounds and vulcanizates showed a lower glass transition temperature (Tg) and better thermal stability than those of the SBR/NO compounds and vulcanizate. The SBR/MSO compounds exhibited faster curing. Their vulcanizates showed lower modulus and higher elongation at break and tensile strength in comparison with the SBR/NO vulcanizates. The dynamic mechanical analysis of SBR/MSO vulcanizates indicated that use of this rubber in tire tread is expected to improve traction but increase rolling resistance compared to the SBR/NO vulcanizates. After adjusting the curative recipe, the modulus and tensile strength and abrasion resistance of the SBR/MSO vulcanizates with low level of modification were tremendously improved with the tensile strength and elongation at break being significantly higher than that of SBR/NO vulcanizate. The use of this recipe is expected to achieve similar traction and lower rolling resistance compared to the SBR/NO recipe. The addition of MSO to SBR has a promising possibility to replace petroleum oils in the rubber along with improvement of safety in tire production
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