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  • ASSOCIATION  (5)
  • SUSCEPTIBILITY  (5)
  • Cervical spine  (3)
  • 1
    Keywords: CANCER ; MODEL ; POPULATION ; RISK ; SITE ; SITES ; GENE ; GENES ; BIOMARKERS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY ; VARIANTS ; HEALTH ; ovarian cancer ; OVARIAN-CANCER ; WOMEN ; REPLICATION ; glycosylation ; ONCOLOGY ; SINGLE NUCLEOTIDE POLYMORPHISMS ; biomarker ; CANCER-RISK ; Genetic ; single nucleotide
    Abstract: Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphism in the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had decreased ovarian cancer risk. The current study attempted to replicate this observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped in 6,965 cases and 8,377 controls from 14 studies forming the Ovarian Cancer Association Consortium. The fixed effects estimate per rs17647532 allele was null (odds ratio, 0.99; 95% confidence interval, 0.92-1.07). When a recessive model was fit, the results were unchanged. Test for hetero geneity of the odds ratios revealed consistency across the 14 replication sites but significant differences compared with the original study population (P = 0.03). This study underscores the need for replication of putative findings in genetic association studies. Cancer Epidemiol Biomarkers Prev; 19(2); 600-4. (C) 2010 AACR
    Type of Publication: Journal article published
    PubMed ID: 20142253
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  • 2
    Keywords: SUSCEPTIBILITY
    Abstract: BACKGROUND: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. METHODS: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. RESULTS: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. CONCLUSIONS: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987-. (c)2013 AACR.
    Type of Publication: Journal article published
    PubMed ID: 23513043
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  • 3
    Keywords: ASSOCIATION ; POLYMORPHISMS ; VARIANTS ; IDENTIFICATION ; METAANALYSIS ; LOCUS
    Abstract: The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22-1.64; P = 5.7 x 10(-6)], rs791587 (HR, 1.36; 95% CI, 1.17-1.57; P = 6.2 x 10(-5)), rs2476491 (HR, = 1.40; 95% CI, 1.19-1.64; P = 5.6 x 10(-5)), and rs10795763 (HR, 1.35; 95% CI, 1.17-1.57; P = 7.9 x 10(-5)), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54-0.82; P = 9.3 x 10(-5)) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer.
    Type of Publication: Journal article published
    PubMed ID: 24764580
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  • 4
    Keywords: CANCER ; PROSTATE ; RISK ; BIOMARKERS ; ASSOCIATION ; SUSCEPTIBILITY ; BREAST ; CONSORTIUM ; MULTIPLE
    Abstract: Background: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI = 1.0-1.4, P-trend = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1.1-1.5, P-trend = 0.003). Methods: We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. Results: No evidence for an association with all cancers or serous cancers was observed in a combined analysis of data from the replication studies (all: OR = 1.0, 95% CI = 0.9-1.1, P-trend = 0.61; serous: OR = 1.0, 95% CI = 0.9-1.1, P-trend = 0.85) or from the combined analysis of discovery and replication studies (all: OR = 1.0, 95% CI = 1.0-1.1, P-trend = 0.28; serous: OR = 1.1, 95% CI = 1.0-1.2, P-trend = 0.11). There was no evidence for statistical heterogeneity in ORs across the studies. Conclusions: Although rs2660753 is a strong prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study. Impact: Our findings, based on a larger sample size, emphasize the importance of replicating potentially promising genetic risk associations.
    Type of Publication: Journal article published
    PubMed ID: 21415361
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  • 5
    Keywords: RISK ; ASSOCIATION ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; statistics ; inflammation ; CARD11 ; FAMILY MEMBERS ; BCL10
    Abstract: Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-kappaB (NF-kappaB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-kappaB family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P 〈 2.5 x 10(-5)). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41-2.35; P = 4.13 x 10(-6)] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 x 10(-5)). Other associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 x 10(-5)) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 x 10(-4)). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies.
    Type of Publication: Journal article published
    PubMed ID: 24740199
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  • 6
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; CELL ; PROSTATE ; RISK ; GENE ; GENES ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY ; SUSCEPTIBILITY LOCUS ; VARIANTS ; DISCOVERY ; STAGE ; ASSAY ; ovarian cancer ; OVARIAN-CANCER ; genetics ; SNP ; COLORECTAL-CANCER ; cancer risk ; GENOTYPES ; CANCER-CELLS ; genotyping ; telomerase ; REPLICATION ; microenvironment ; case-control study ; ASSOCIATIONS ; VARIANT ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SCIENCE ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; GENOTYPE ; LOCUS ; INCREASED RISK ; CANCER-RISK ; OVARIAN ; 8Q24 ; MYC ; GENOME-WIDE ASSOCIATION ; CONSORTIUM ; Genetic ; CONTRIBUTE ; single nucleotide ; INCESSANT OVULATION
    Abstract: 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
    Type of Publication: Journal article published
    PubMed ID: 20628624
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  • 7
    ISSN: 1279-8517
    Keywords: Cervical spine ; Uncinate process ; Radiculopathy ; Decompression ; Anatomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Morphometric evaluation of 54 dry cervical spines from C3 to C7 (a total of 270 cervical vertebrae) was performed to determine the bony boundaries of the uncinate process for resection of the uncinate process for access to posterolateral osteophytes or herniated disks at the time of anterior cervical diskectomy. The uncinate processes were significantly higher (p 〈 0.01) at the C4 - C6 levels (5.8 ± 1.1 mm to 6.1 ± 1.3 mm) than at the C3 or C7 levels. The distance between the medial and lateral margins of the base of the uncinate process was significantly smaller (p 〈 0.01) at the C3 level (4.9 ± 0.7 mm) than at the C7 level (6.3 ± 0.7 mm). The anteroposterior diameter of the medial margin of the uncinate process decreased gradually from the C5 (12.5 ± 1.5 mm) to C7 levels (11.6 ± 1.3 mm) (p 〈 0.05). The inter-uncinate distance widened from the C3 (19.2 ± 1.5 mm) to the C7 (24.6 ± 2.1 mm) levels (p 〈 0.01). The mid-anteroposterior diameter of vertebral body increased gradually from the C3 (14.7 ± 1.1 mm) to the C7 levels (16.1 ± 1.5 mm) (p 〈 0.01). The width of the vertebra increased gradually from C3 to C7 (from 19.2 ± 1.8 mm at C3 to 25.6 ± 2.0 mm at C7) (p 〈 0.01). Knowledge of all the aforementioned data may be helpful during anterolateral cervical uncosectomy or uncoforaminotomy.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1279-8517
    Keywords: Cervical spine ; Uncinate process ; Radiculopathy ; Decompression ; Anatomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Nous avons réalisé l'évaluation morphométrique de 54 colonnes cervicales sèches de C3 à C7 (soit un total de 270 vertèbres cervicales) pour déterminer les limites osseuses du processus unciné, avec application à sa résection pour accéder aux ostéophytes postéro-latéraux ou à une hernie discale au cours d'une discectomie cervicale antérieure. Les processus unciné étaient significativement plus hauts (p〈0,01) aux niveaux C4–C6 (de 5,8 ± 1,1 mm, à 6,1 ± 1,3 mm) qu'aux niveaux C3 ou C7. La distance séparant les bords médial et latéral de la base du processus unciné était significativement plus petite (p〈0,01) au niveau C3 (4,9 ± 0,7 mm) qu'au niveau C7 (6,3 ± 0,7 mm). Le diamètre sagittal du bord médial du processus unciné diminuait graduellement du niveau C5 (12,5 ± 1,5 mm) au niveau C7 (11,6 ± 1,3 mm) (p〈0,05). La distance séparant les processus uncinés augmentait du niveau C3 (19,2 ± 1,5 mm) au niveau C7 (24,6 ± 2,1 mm) (p〈0,01). Le diamètre sagittal médian du corps vertébral augmentait graduellement du niveau C3 (14,7 ± 1,1 mm) au niveau C7 (16,1 ± 1,5 mm) (p〈0,01). La largeur de la vertèbre augmentait graduellement du niveau C3 (19,2 ± 1,8 mm) au niveau C7 (25,6 ± 2,0 mm) (p〈0,01). Les renseignements ainsi obtenus peuvent être utiles au cours des uncusectomies et des uncusoforaminotomies cervicales antéro-latérales.
    Notes: Summary Morphometric evaluation of 54 dry cervical spines from C3 to C7 (a total of 270 cervical vertebrae) was performed to determine the bony boundaries of the uncinate process for resection of the uncinate process for access to posterolateral osteophytes or herniated disks at the time of anterior cervical diskectomy. The uncinate processes were significantly higher (p〈0.01) at the C4 – C6 levels (5.8 ± 1.1 mm to 6.1 ± 1.3 mm) than at the C3 or C7 levels. The distance between the medial and lateral margins of the base of the uncinate process was significantly smaller (p〈0.01) at the C3 level (4.9 ± 0.7 mm) than at the C7 level (6.3 ± 0.7 mm). The anteroposterior diameter of the medial margin of the uncinate process decreased gradually from the C5 (12.5 ± 1.5 mm) to C7 levels (11.6 ± 1.3 mm) (p〈0.05). The interuncinate distance widened from the C3 (19.2 ± 1.5 mm) to the C7 (24.6 ± 2.1 mm) levels (p〈0.01). The mid-anteroposterior diameter of vertebral body increased gradually from the C3 (14.7 ± 1.1 mm) to the C7 levels (16.1 ± 1.5 mm) (p〈0.01). The width of the vertebra increased gradually from C3 to C7 (from 19.2 ± 1.8 mm at C3 to 25.6 ± 2.0 mm at C7) (p〈0.01). Knowledge of all the aforementioned data may be helpful during anterolateral cervical uncosectomy or uncoforaminotomy.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1279-8517
    Keywords: Cervical spine ; Discectomy ; Anterior approach ; Fusion ; Anatomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé 20 colonnes cervicales issues de cadavres d'adultes ont été sectionnées longitudinalement sur la ligne médiane pour fournir des coupes longitudinales des corps vertébraux et des disques intervertébraux de C3 à T1. Les images anatomiques obtenues ont été traitées à l'aide d'un ordinateur pour fournir des mesures des disques intervertébraux et des corps vertébraux. L'épaisseur antéropostérieure (AP) augmentait progressivement de 16,56±2,21 mm en C3 à 19,32±2,30 mm en C7. Les valeurs les plus importantes de l'épaisseur AP au plateau vertébral inférieur ont été relevées en C5 (20,75±2,87 mm) et C6 (20,56±2,31 mm) alors qu'elles étaient plus faibles en C3 (18,26±1,82 mm), C4 (19,27±2,88 mm), et C7 (19,21±3,22 mm). L'épaisseur AP mesurée au plateau vertébral supérieur était plus importante que celle mesurée au plateau inférieur. La hauteur du disque intervertébral était moins élevée à la partie postérieure des disques intervertébraux de C2–C3 à C7-T1 (2,95±0,86 mm en C2–C3, 2,78±0,93 mm en C3–C4, 2,45±0,79 mm en C4–C5, 2,92±0,64 mm en C5–C6, 2,46±0,59 mm en C6–C7, et 2,93±1,05 mm en C7-T1) en comparaison avec celles relevées à la partie antérieure de l'espace de C2–C3 à C7-T1 (4,07±0,85 mm en C2–C3, 4,34±1,18 mm en C3–C4, 3,95±1,37 mm en C4–C5, 3,55±1,37 mm en C5–C6, 3,55±0,76 mm en C6–C7, et 3,67±1,19 mm en C7-T1). L'axe moyen du disque intervertébral était situé environ 3 mm audessus du point moyen antérieur de l'annulus fibrosus au niveau de la partie inférieure de la colonne cervicale. Pour atteindre la partie postérieure de l'espace intervertébral, à partir du point moyen antérieur de l'annulus fibrosus, il faut donner à la mèche une angulation de 5° vers la tête par rapport à l'axe moyen du disque intervertébral. Toutes ces données cadavériques originales peuvent rendre service au cours des abords antérieurs pour discectomie, vertébrectomie, et mise en place de plaque et de vis.
    Notes: Summary Twenty adult cadaveric cervical spines were sectioned longitudinally through the midline to display longitudinal sections of the vertebral bodies and disc spaces from C3 to T1. Computer-assisted anatomic images were obtained for measurements of the disc spaces and vertebral bodies. Anteroposterior (AP) depth gradually increased from 16.56±2.21 mm at C3 to 19.32±2.30 mm at C7. Greater values of AP depth at the inferior endplate were found at C5 (20.75±2.87 mm) and C6 (20.56±2.31 mm) compared with the values at C3 (18.26±1.82 mm), C4 (19.27±2.88 mm) and C7 (19.21±3.22 mm). The AP depth at the superior endplate was greater than that at the inferior endplate. The height of the disc space was found to be lowest at the posterior disc space from C2–3 to C7-T1 (2.95±0.86 mm at C2–3, 2.78±0.93 mm at C3–4, 2.45±0.79 mm at C4–5, 2.92±0.64 mm at C5–6, 2.46±0.59 mm at C6–7, 2.93±1.05 mm at C7-T1), when compared to the height of the disc space at the anterior disc space from C2–3 to C7-T1 (4.07±0.85 mm at C2–3, 4.34±1.18 mm at C3–4, 3.95±1.37 mm at C4–5, 3.55±1.37 mm at C5–6, 3.55±0.76 mm at C6–7, 3.67±1.17 mm at C7-T1). The mid-axis of the disc space was situated at approximately 3 mm above the anterior midpoint of the annulus fibrosus at the level of the lower cervical spine. To reach the posterior portion of the disc space from the anterior midpoint of the annulus fibrosus, a 5° cephalad angulation of the drill relative to the midaxis of the disc space is necessary. All these original data from cadavers may be helpful during anterior approach for discectomy, vertebrectomy and anterior screw-plate placement.
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