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  • 1
    Keywords: CANCER ; tumor ; MODEL ; DISEASE ; POPULATION ; RISK ; GENES ; REED-STERNBERG CELLS ; CLASS-I ; ENDOPLASMIC-RETICULUM ; PSORIASIS ; INFECTIOUS-MONONUCLEOSIS ; susceptibility loci ; DISEASE HD
    Abstract: Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification. We conducted a genome-wide association study of 1200 cHL patients and 6417 control subjects, with validation in an independent replication series, to identify common genetic variants associated with total cHL and subtypes defined by tumor EBV status. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) assuming a log-additive genetic model for the variants. All statistical tests were two-sided. Two novel loci associated with total cHL irrespective of EBV status were identified in the major histocompatibility complex region; one resides adjacent to MICB (rs2248462: OR = 0.61, 95% CI = 0.53 to 0.69, P = 1.3 x 10(-13)) and the other at HLA-DRA (rs2395185: OR = 0.56, 95% CI = 0.50 to 0.62, P = 8.3 x 10(-25)) with both results confirmed in an independent replication series. Consistent with previous reports, associations were found between EBV-positive cHL and genetic variants within the class I region (rs2734986, HLA-A: OR = 2.45, 95% CI = 2.00 to 3.00, P = 1.2 x 10(-15); rs6904029, HCG9: OR = 0.46, 95% CI = 0.36 to 0.59, P = 5.5 x 10(-10)) and between EBV-negative cHL and rs6903608 within the class II region (rs6903608, HLA-DRA: OR = 2.08, 95% CI = 1.84 to 2.35, P = 6.1 x 10(-31)). The association between rs6903608 and EBV-negative cHL was confined to the nodular sclerosis histological subtype. Evidence for an association between EBV-negative cHL and rs20541 (5q31, IL13: OR = 1.53, 95% CI = 1.32 to 1.76, P = 5.4 x 10(-9)), a variant previously linked to psoriasis and asthma, was observed; however, the evidence for replication was less clear. Notably, one additional psoriasis-associated variant, rs27524 (5q15, ERAP1), showed evidence of an association with cHL in the genome-wide association study (OR = 1.21, 95% CI = 1.10 to 1.33, P = 1.5 x 10(-4)) and replication series (P = .03). Overall, these results provide strong evidence that EBV status is an etiologically important classification of cHL and also suggest that some components of the pathological process are common to both EBV-positive and EBV-negative patients
    Type of Publication: Journal article published
    PubMed ID: 22286212
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  • 2
    Abstract: To identify susceptibility loci for classical Hodgkin`s lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 x 10(-8)), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 x 10(-13)) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 x 10(-8)). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 x 10(-50)). These data provide new insight into the pathogenesis of cHL.
    Type of Publication: Journal article published
    PubMed ID: 21037568
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 70 (1986), S. 60-70 
    ISSN: 1432-0533
    Keywords: Fetal nerve ; Sural nerve ; Nerve development ; Myelination ; Nerve morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A morphometric study was performed on sural nerves from human fetuses at 15 to 36 weeks postovulation. There were no myelinated fibres at 15 and 16 weeks, but by 21 weeks there were 5,000/mm2, rising to 25,000/mm2 at 36 weeks. During the fetal period, the mean myelin lamellar count trebled and the g ratio (axon diameter: total fibre diameter) decreased from 0.90 to 0.75, although the axon diameter of myelinated fibres did not increase. The smallest myelinated axon diameter was 0.63 μm, whereas the largest unmyelinated axon in a 1:1 relationship with a Schwann cell was 2.83 μm, suggesting that axon size is unlikely to be the only stimulus for myelination. The density of unmyelinated axons that were the sole occupants of a Schwann cell fell considerably between 23 and 33 weeks, while the ratio of total unmyelinated axons to myelinated fibres decreased from 82:1 at 21 weeks to 6:1 at 36 weeks. Data for Schwann cell nuclear density and percentages of fibres cut through the nucleus are also presented.
    Type of Medium: Electronic Resource
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