Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • SUSCEPTIBILITY  (8)
  • 1
    Keywords: CANCER ; MODEL ; PROSTATE ; DISEASE ; RISK ; GENE ; MARKER ; IMPACT ; BIOMARKERS ; ASSOCIATION ; LINKAGE ; polymorphism ; single nucleotide polymorphism ; SUSCEPTIBILITY ; VARIANTS ; STAGE ; IDENTIFICATION ; HEALTH ; SNP ; PROSTATE-CANCER ; MARKERS ; LINKAGE DISEQUILIBRIUM ; diabetes ; REPLICATION ; FUTURE ; DIABETES-MELLITUS ; ONCOLOGY ; VARIANT ; METAANALYSIS ; biomarker ; methods ; MULTIETHNIC COHORT ; LINKAGE-DISEQUILIBRIUM ; 8Q24 ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; genetic association ; SCAN ; Genetic ; COMMON VARIANTS ; Type ; single nucleotide ; RISK-ASSOCIATED LOCI
    Abstract: Background: Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P = 2.14 x 10(-6)), with a suggestion of stronger association with aggressive disease (P = 1.2 x 10(-7)). Methods: In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry. Results: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P = 7.79 x 10(-11); ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P = 1.60 x 10(-4) for aggressive cancer, n = 4,597; P = 3.25 x 10(-8) for non-aggressive cancer, n = 4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P = 0.587), body stature (rs849141, tagged by rs849136; P = 0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P = 0.657). Conclusion: rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry. Impact: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa. Cancer Epidemiol Biomarkers Prev; 19(5); 1349-55. (C)2010 AACR
    Type of Publication: Journal article published
    PubMed ID: 20406958
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: TUMORS ; mechanisms ; ASSOCIATION ; SUSCEPTIBILITY ; ABERRATIONS ; MUTATIONS ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; ANEUPLOIDY ; GENOMIC IMBALANCES ; MAFFUCCI SYNDROME ; OLLIER DISEASE
    Abstract: In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of 〉 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases
    Type of Publication: Journal article published
    PubMed ID: 22561519
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: CANCER ; PROSTATE ; COMMON ; CT ; SUPPORT ; COHORT ; POPULATION ; RISK ; GENE ; ASSOCIATION ; LINKAGE ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY ; ALPHA ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; ENCODES ; HEALTH ; WOMEN ; SNP ; MEN ; prostate cancer ; PROSTATE-CANCER ; LINE ; REGION ; LINKAGE DISEQUILIBRIUM ; POPULATIONS ; POSTMENOPAUSAL WOMEN ; SINGLE ; DEFICIENCY ; ONCOLOGY ; ASSOCIATIONS ; SNPs ; CANCER SUSCEPTIBILITY ; METAANALYSIS ; biomarker ; INTERVAL ; HAPLOTYPE ; HAPLOTYPES ; single-nucleotide ; USA ; HORMONES ; STEROID-HORMONES ; odds ratio ; cancer research ; MULTIETHNIC COHORT ; PREDICT ; steroids ; postmenopausal ; block ; HORMONE-LEVELS ; EXONS ; GENETIC-VARIATION ; ANDROGEN RECEPTOR GENE ; BRAZILIAN PATIENTS ; SERUM ANDROGENS
    Abstract: CYP17 encodes cytochrome p450c17 alpha, which mediates activities essential for the production of sex steroids. Common germ line variation in the CYP17 gene has been related to inconsistent results in breast and prostate cancer, with most studies focusing on the nonsynonymous single nucleotide polymorphism (SNP) T27C (rs743572). We comprehensively characterized variation in CYP17 by direct sequencing of exons followed by dense genotyping across the 58 kb region around CYP17 in five racial/ethnic populations. Two blocks of strong linkage disequilibrium were identified and nine haplotype-tagging SNPs, including T27C, were chosen to predict common haplotypes (R-h(2) 〉= 0.85). These haplotype-tagging SNPs were genotyped in 8,138 prostate cancer cases and 9,033 controls, and 5,333 breast cancer cases and 7,069 controls from the Breast and Prostate Cancer Cohort Consortium. We observed borderline significant associations with prostate cancer for rs2486758 [TC versus TT, odds ratios (OR), 1.07; 95% confidence intervals (95% Cl), 1.00-1.14; CC versus TT, OR, 1.09; 95% CI, 0.95-1.26; P trend = 0.04] and rs6892 (AG versus AA, OR, 1.08; 95% CI, 1.00-1.15; GG versus AA, OR, 1.11; 95% CI, 0.95-1.30; P trend = 0.03). We also observed marginally significant associations with breast cancer for rs4919687 (GA versus GG, OR, 1.04; 95% CI, 0.97-1.12, AA versus GG, OR, 1.17; 95% CI, 1.03-1.34; P trend = 0.03) and rs4919682 (CT versus CC, OR, 1.04; 95% CI, 0.97-1.12; TT versus CC, OR, 1.16; 95% CI, 1.01-1.33; P trend = 0.04). Common variation at CYP17 was not associated with circulating sex steroid hormones in men or postmenopausal women. Our findings do not support the hypothesis that common germ line variation in CYP17 makes a substantial contribution to postmenopausal breast or prostate cancer susceptibility
    Type of Publication: Journal article published
    PubMed ID: 18006912
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: CANCER ; PROSTATE ; RISK ; MARKER ; ASSOCIATION ; SUSCEPTIBILITY ; SUSCEPTIBILITY LOCUS ; IDENTIFICATION ; genetics ; COLORECTAL-CANCER ; prostate cancer ; PROSTATE-CANCER ; MARKERS ; cancer risk ; VARIANT ; CANCER SUSCEPTIBILITY ; CORE ; LOCUS ; USA ; CANCER-RISK ; 8Q24 ; GENOME-WIDE ASSOCIATION ; SCAN ; Genetic ; Genome-wide association studies ; RANGE ; MULTIPLE LOCI
    Abstract: We report a genome-wide association study in 10,286 cases and 9,135 controls of European ancestry in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. We identify a new association with prostate cancer risk on chromosome 8q24 (rs620861, P = 1.3 x 10(-10), heterozygote OR = 1.17, 95% CI 1.10-1.24; homozygote OR = 1.33, 95% CI 1.21-1.45). This defines a new locus associated with prostate cancer susceptibility on 8q24
    Type of Publication: Journal article published
    PubMed ID: 19767755
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: CANCER ; POPULATION ; RISK ; GENE-EXPRESSION ; SUSCEPTIBILITY ; VARIANTS ; IDENTIFICATION ; METAANALYSIS ; LOCUS ; 8Q24 ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; MULTIPLE LOCI ; HEPATOCYTE NUCLEAR FACTOR-1-BETA
    Abstract: Previous genome-wide association studies have identified two independent variants in HNF1B as susceptibility loci for prostate cancer risk. To fine-map common genetic variation in this region, we genotyped 79 single nucleotide polymorphisms (SNPs) in the 17q12 region harboring HNF1B in 10 272 prostate cancer cases and 9123 controls of European ancestry from 10 case-control studies as part of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P 〈 5 x 10(-8) with the most significant association with rs4430796 (P = 1.62 x 10(-24)). However, risk within this first locus was not entirely explained by rs4430796. Although modestly correlated (r(2) = 0.64), rs7405696 was also associated with risk (P = 9.35 x 10(-23)) even after adjustment for rs4430769 (P = 0.007). As expected, rs11649743 was related to prostate cancer risk (P = 3.54 x 10(-8)); however, the association within this second locus was stronger for rs4794758 (P = 4.95 x 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (P = 0.32 for rs11649743; P = 0.002 for rs4794758). Sequential conditional analyses indicated that five SNPs (rs4430796, rs7405696, rs4794758, rs1016990 and rs3094509) together comprise the best model for risk in this region. This study demonstrates a complex relationship between variants in the HNF1B region and prostate cancer risk. Further studies are needed to investigate the biological basis of the association of variants in 17q12 with prostate cancer
    Type of Publication: Journal article published
    PubMed ID: 21576123
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: CANCER ; human ; PATHWAY ; PATHWAYS ; DISEASE ; EPIDEMIOLOGY ; POPULATION ; RISK ; GENE ; GENES ; TUMOR-NECROSIS-FACTOR ; ASSOCIATION ; polymorphism ; SUSCEPTIBILITY ; LYMPHOMA ; case-control studies ; INDIVIDUALS ; ALCOHOL-CONSUMPTION ; B-CELL LYMPHOMA ; FACTOR-ALPHA ; CYTOKINE ; case-control study ; case control studies ; single-nucleotide ; single-nucleotide polymorphism ; GENOTYPE DATA ; pooled analysis ; INTERLEUKIN-10 ; PROMOTER POLYMORPHISMS ; BIOLOGICAL IMPLICATIONS
    Abstract: Background Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph). Methods We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model. Findings The tumour necrosis factor (TNF) -308G -〉 A polymorphism was associated with increased risk of nonHodgkin lymphoma (p for trend=0 . 005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1 . 29 [95% CI 1 . 10-1 . 51] for GA and 1.65 [1 . 16-2 . 34] for AA, p for trend 〈 0 . 0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T -〉 A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0 . 02), again particularly for diffuse large B-cell lymphoma (p for trend=0 . 006). For individuals homozygous for the TNF -308A allele and carrying at least one IL 10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2 . 13 [1 . 37-3 . 32], p=0 . 00083). Interpretation Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer
    Type of Publication: Journal article published
    PubMed ID: 16389181
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: CANCER ; RISK ; SUSCEPTIBILITY ; HEIGHT ; susceptibility loci ; SEQUENCE VARIANTS ; FGF10
    Abstract: Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 x 10(-8) to P = 2.7 x 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining similar to 25% of the familial risk in this disease, have now been identified
    Type of Publication: Journal article published
    PubMed ID: 21743467
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: DEATH ; DISEASE ; MORTALITY ; SUSCEPTIBILITY ; MEN ; LOCI ; 8Q24 ; GENOME-WIDE ASSOCIATION ; GENETIC-VARIANTS
    Abstract: BACKGROUND: Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM). OBJECTIVE: To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM. DESIGN, SETTING, AND PARTICIPANTS: We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls. RESULTS AND LIMITATIONS: Among the cases, we found that 8 of the 47 SNPs were significantly associated (p〈0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p〈0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only. CONCLUSIONS: Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. PATIENT SUMMARY: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction.
    Type of Publication: Journal article published
    PubMed ID: 24411283
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...