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  • 1
    Keywords: CANCER ; SURVIVAL ; BLOOD ; human ; COHORT ; MORTALITY ; RISK ; GENE ; GENES ; ASSOCIATION ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; DESIGN ; genetics ; SNP ; RATES ; case-control studies ; INDIVIDUALS ; pancreatic cancer ; MAPS ; case control study ; case-control study ; WORLDWIDE ; PANCREATIC-CANCER ; VARIANT ; SNPs ; EPIDEMIOLOGIC EVIDENCE ; USA ; prospective ; BASE-LINE CHARACTERISTICS ; BLOOD-GROUP ; GENOME-WIDE ASSOCIATION ; WOMENS HEALTH ; Genetic ; Genome-wide association studies ; ALLERGIES ; CONFIDENCE ; RATIONALE
    Abstract: We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based casecontrol study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B
    Type of Publication: Journal article published
    PubMed ID: 19648918
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  • 2
    Keywords: CANCER ; CELLS ; LUNG ; MODEL ; FOLLOW-UP ; COHORT ; cohort study ; RISK ; GENE ; ASSOCIATION ; SUSCEPTIBILITY ; VARIANTS ; BREAST-CANCER ; AGE ; genetics ; PROSPECTIVE COHORT ; REGION ; telomerase ; case-control study ; PANCREATIC-CANCER ; prospective ; BASE-LINE CHARACTERISTICS ; GENOME-WIDE ASSOCIATION ; WOMENS HEALTH ; Genetic ; RECOMBINATION HOTSPOTS
    Abstract: We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies
    Type of Publication: Journal article published
    PubMed ID: 20101243
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  • 3
    Keywords: CANCER ; BLOOD ; MODEL ; SYSTEM ; COHORT ; DISEASE ; incidence ; POPULATION ; RISK ; GENE ; ASSOCIATION ; VARIANTS ; PROSPECTIVE COHORT ; smoking ; GENOTYPES ; SMOKERS ; pancreatic cancer ; ONCOLOGY ; REGRESSION ; ASSOCIATIONS ; PANCREATIC-CANCER ; ALLELES ; GENOTYPE ; LOCUS ; prospective ; CANCER-RISK ; GENETIC-BASIS ; GENOME-WIDE ASSOCIATION ; BOSTON ; Type ; COHORTS ; STRATIFICATION ; GROUP ANTIGENS
    Abstract: A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18-1.62], 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk. Cancer Res; 70(3); 1015-23. (C)2010 AACR
    Type of Publication: Journal article published
    PubMed ID: 20103627
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  • 4
    Keywords: CANCER ; COHORT ; RISK ; ASSOCIATION ; SUSCEPTIBILITY ; HEALTH ; DESIGN ; WOMEN ; MEN ; cancer risk ; NETHERLANDS ; UNITED-STATES ; TOBACCO ; ALCOHOL ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; pancreatic cancer ; NESTED CASE-CONTROL ; LIFE-STYLE FACTORS ; ONCOLOGY ; case-control study ; REGRESSION ; ASSOCIATIONS ; PANCREATIC-CANCER ; pooled analysis ; CANCER-RISK ; BASE-LINE CHARACTERISTICS ; nested case-control study ; GENOME-WIDE ASSOCIATION ; WOMENS HEALTH ; COFFEE CONSUMPTION ; Type ; nested case control study
    Abstract: The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. 〉 0 to 〈 5 g/day). A statistically significant increase in risk was observed among men consuming 45 or more grams of alcohol from liquor per day (OR = 2.23, 95% CI = 1.02-4.87, compared to 0 g/day of alcohol from liquor, P-trend = 0.12), but not among women (OR = 1.35, 95% CI = 0.63-2.87, for 30 or more g/day of alcohol from liquor, compared to none). No associations were noted for wine or beer intake. Overall, no significant increase in risk was observed, but a small effect among heavy drinkers cannot be ruled out
    Type of Publication: Journal article published
    PubMed ID: 20373013
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  • 5
    Keywords: CANCER ; MODEL ; LUNG-CANCER ; COHORT ; EXPOSURE ; RISK ; RISK-FACTORS ; CARCINOGENESIS ; ASSOCIATION ; TRIAL ; prevention ; PATTERNS ; HEALTH ; CIGARETTE-SMOKING ; MEN ; smoking ; RISK FACTOR ; case-control studies ; pancreatic cancer ; NESTED CASE-CONTROL ; case-control study ; REGRESSION ; pancreas ; PANCREATIC-CANCER ; intensity ; METAANALYSIS ; pooled analysis ; USA ; smoking cessation ; RISK-FACTOR ; pancreatic neoplasms ; LOGISTIC-REGRESSION ; CONSORTIUM ; CONFIDENCE ; MODELING TOTAL EXPOSURE ; SHANGHAI ; tobacco use cessation
    Abstract: Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (〉= 30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (〉= 50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (〉= 40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis
    Type of Publication: Journal article published
    PubMed ID: 19561064
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  • 6
    ISSN: 0887-6134
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of 35 steroid conjugates (sulfates and glucuronides) and bile salts were investigated by using fast atom bombardment and tandem mass spectrometry. Collisional activation of the [M - H]- anions of sulfate conjugates and bile salts predominantly yields fragment ions arising by reactions occurring remote from the charge site. These reactions are sometimes sensitive to differences in stereochemistry at positions remote from the charge site and are useful for positional isomer differentiation. On the other hand, collisional activation of the [M - H]- anions of the glucouronide conjugates leads primarily to charge-driven fragementations.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0887-6134
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Four β-endorphins (β-endorphin 6-17, 2-17, 1-16, and 1-17) and two adrenocorticotropic hormone (ACTH) peptides (ACTH 1-10 and (1-16)-NH2) were studied by using fast atom bombardment coupled with tandem mass spectrometry. The capability to reproduce metastable ion and collisionally activated decomposition spectra on two different commercial sector mass spectrometers in two different laboratories was found to be acceptable (deviations in relative abundance are less than ± 50%). The endorphin peptides fragment metastably or upon collisional activation to give abundant B-series ions as well as Y-series ions, whereas Y-series ions are the principal ionic species produced upon the desorption by fast atom bombardment. The ACTH peptides also fragment to give Y-series ions, but of relatively low abundance compared to those from the endorphins. For both sets of peptides, high-energy collisionally activated decomposition and metastable ion decomposition daughter ion spectra are precise, structurally informative - even for peptides up to m/z 2000 - and complementary to spectra of daughter ions produced by desorption ionization alone.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: Sequential daughter-ion-scanning analyses of small peptides have been performed using a hybrid tandem instrument of BEqQ configuration. Precursor ions are selected by B and allowed or induced (by high-energy collisional activation) to decompose in the region preceding E. Decoupling of E from the accelerating voltage permits the selection of the first-generation daughter ion whilst retaining appropriate float voltages for the quadrupole assemblies. The daughter ion selected by E is further subjected to low-energy collisional-activation dissociation (CAD) in q and the fragment-ion spectrum is obtained by scanning Q. The sequential daughter-ion-scanning technique has been used to establish that ‘internal’ fragments of the types, (AY′) and (BY′), are formed via initial Y-type cleavage. Fragmentation of a protonated peptide (angiotensin III) by loss of the C-terminal amino acid residue, yielding a (Bn′ + OH) ion, is reported for the first time. This process is analogous to that previously described for metal-cationized peptides.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1040-0397
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of 12 macrocycles containing 4, 6, or 8 N, S, and O heteroatoms (with increasing size from 14 to 24 atoms in the cycle) was studied to ascertain size and heteroatoms effects on the formation and 14 redox characteristics of their mercuric complexes. The concentration dependence of anodic currents at mercury electrodes in solutions of these ligands led to the determination of the formation constants of the complexes generated according to the folling of \documentclass{article}\pagestyle{empty}\begin{document}$$ {\rm Hg} \mathbin{\lower.3ex\hbox{$\buildrel\textstyle\rightarrow\over {\smash{\leftarrow}\vphantom{_{\vbox to.5ex{\vss}}}}$}} {\rm Hg}^{{\rm 2 + }} {\rm + 2e}^{\rm - } {\rm,}\,{\rm Hg}^{{\rm 2 + }} {\rm + jL} \mathbin{\lower.3ex\hbox{$\buildrel\textstyle\rightarrow\over {\smash{\leftarrow}\vphantom{_{\vbox to.5ex{\vss}}}}$}} {\rm (HgL}_{\rm j} {\rm)}^{{\rm 2 + }} $$\end{document} In propylene carbonate, the resulting mercuric complexes were stable (log Ks up to 40) mono- and dinuclear species. Their stability depends both on the nature of the heteroatoms and on the size of the macrocycle. For identical ligand sizes, the stability sequence N 〉 S 〉 O was established for mercuric complexes.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1040-0397
    Keywords: Amalgam electrode ; cadmium ; macrocyclic complexes ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The electrochemical oxidation of cadmium amalgam was studied in the nonaqueous solvents CH2Cl2, 1,2-C2H4Cl2 and propylene carbonate. Significant coordination effects were observed between the electrogenerated Cd(II) ions and 18-membered macromonocyclic ligands, each containing six Lewis bases heteroatoms: 18-O6, 18-S6, 18-N2O4, and 18-N6. The stoichiometries and the stabilities of the resulting complexes were determined. These stabilities increase from 18-O6 or 18-S6 to 18-N6.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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