Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Keywords: EXPRESSION ; carcinoma ; polymorphism ; BREAST-CANCER ; COLON-CANCER ; GENOME-WIDE ASSOCIATION ; UDP-GLUCURONOSYLTRANSFERASES ; IRON TRANSPORT ; FAMILY SLC25 ; HEPHAESTIN
    Abstract: BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q〈0.2 was applied to adjust for multiple comparisons. RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p〈0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
    Type of Publication: Journal article published
    PubMed ID: 26091520
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: EXPRESSION ; carcinoma ; RISK ; ORAL-CONTRACEPTIVES ; GROWTH-FACTOR-BETA ; TRENDS ; MAMMARY-GLAND ; TGF-BETA ; DECORIN ; GENOME-WIDE ASSOCIATION
    Abstract: Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U. S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (P-heterogeneity 〉= 0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; P-trend = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (P-heterogeneity 〉= 0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; P-trend 〈= 0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P-heterogeneity 〈= 0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P-interaction 〈= 0.003), age at diagnosis (P-interaction=0.04), and year of diagnosis (P-interaction=0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required
    Type of Publication: Journal article published
    PubMed ID: 21637745
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: PEPTIDE ; EXPRESSION ; TOOL ; RISK ; VARIANTS ; CLASS-I ; SNPs ; RESOURCE ; SET ; UNIVERSITY
    Abstract: Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 x 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 x 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 x 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 x 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 x 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRbeta1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 x 10(-67) to 2.67 x 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 x 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 x 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
    Type of Publication: Journal article published
    PubMed ID: 25279986
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: EXPRESSION ; VARIANTS ; BREAST ; IDENTIFICATION ; Hox genes ; GENOME-WIDE ASSOCIATION ; RISK LOCI ; LONG-RANGE INTERACTION ; ANALYSES REVEAL ; FALLOPIAN-TUBE
    Abstract: Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P 〈= 10(-5)). For three cis-eQTL associations (P〈1.4 x 10(-3), FDR〈0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P = 6 x 10(-10) for risk variants (P〈10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
    Type of Publication: Journal article published
    PubMed ID: 26391404
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    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 ...
  • 6
    Keywords: RISK ; GENE ; GENES ; ASSOCIATION ; polymorphism ; SUSCEPTIBILITY ; LYMPHOMA ; PROMOTER ; meta-analysis ; FOLLICULAR LYMPHOMA ; SYSTEMIC-LUPUS-ERYTHEMATOSUS ; VARIANT ; RHEUMATOID-ARTHRITIS ; ALLELES ; pooled analysis ; B-CELL ; SUBGROUPS ; INTERLEUKIN-10 ; SUN EXPOSURE ; GENETIC-VARIATION ; non-Hodgkin ; Genetic ; IMMUNE ; single nucleotide ; lymphotoxin-alpha ; tumor necrosis factor-alpha
    Abstract: In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G 〉 A (rs1800629), lymphotoxin-alpha (LTA) 252A 〉 G (rs909253), IL10 -3575T 〉 A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (ORallelic) = 1.10, P-trend = 0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic = 1.23, P-trend = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: ORallelic = 1.13, P-trend = 0.0001; DLBCL: ORallelic = 1.25, P-trend = 3.7 x 10(-6); marginal zone lymphoma: ORallelic = 1.35, P-trend = 0.004) and LTA 252G carriers (DLBCL: ORallelic = 1.12, P-trend = 0.006; mycosis fungoides: ORallelic = 1.44, P-trend = 0.015). The LTA 252A 〉 G/TNF -308G 〉 A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T 〉 A and DLBCL (P-trend = 0.02) and IL10 -1082A 〉 G and mantle cell lymphoma (P-trend = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A 〉 G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology
    Type of Publication: Journal article published
    PubMed ID: 20047977
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: CELLS ; EXPRESSION ; carcinoma ; RISK ; GENE ; leukemia ; MYC ; GENOME-WIDE ASSOCIATION ; NEBULETTE ; 19P13
    Abstract: Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 x 10(-9)) and 10p12 (rs1243180, P = 1.8 x 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 x 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.
    Type of Publication: Journal article published
    PubMed ID: 23535730
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: GENE ; MOLECULAR CHARACTERIZATION ; SUSCEPTIBILITY LOCUS ; VARIANTS ; IDENTIFICATION ; microsatellite instability ; MUTATIONS ; endometriosis ; CLEAR-CELL CARCINOMA ; GRADE SEROUS CARCINOMA
    Abstract: Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P 〈 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P 〈 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.
    Type of Publication: Journal article published
    PubMed ID: 24190013
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...