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  • 1
    Keywords: CANCER ; POPULATION ; RISK ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; FOLLICULAR LYMPHOMA ; TUMORIGENESIS ; NON-HODGKIN-LYMPHOMA ; COMMON VARIANTS ; NECROSIS-FACTOR TNF ; RAL GTPASES
    Abstract: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10-21), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10-10), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10-8) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10-13 and 3.63 x 10-11, respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
    Type of Publication: Journal article published
    PubMed ID: 25261932
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  • 2
    Keywords: CANCER ; EXPRESSION ; Germany ; neoplasms ; DIAGNOSIS ; POPULATION ; RISK ; DISTINCT ; PROTEIN ; PROTEINS ; SAMPLE ; SAMPLES ; PATIENT ; RESPONSES ; INFECTION ; SERA ; ANTIGEN ; ANTIGENS ; T-CELL ; antibodies ; antibody ; ENTRY ; virus ; LYMPHOMA ; MALIGNANCIES ; PATTERNS ; AGE ; COUNTRIES ; DIVERSITY ; CANCER-PATIENTS ; case-control studies ; ANTIBODY-RESPONSES ; EPITOPE ; EPITOPES ; SERIES ; IMBALANCES ; CANCER PATIENTS ; EPSTEIN-BARR-VIRUS ; HODGKINS-DISEASE ; FOLLICULAR LYMPHOMA ; SERUM ; ELISA ; Epstein-Barr virus ; MALIGNANCY ; ONCOLOGY ; DISORDERS ; case control study ; case-control study ; SUBSET ; PATTERN ; BZLF1 ; VIRUS-INFECTION ; EBV INFECTION ; LEVEL ; case control studies ; INTERVAL ; analysis ; EVENTS ; leukaemia ; USA ; LOSSES ; EBV ; EVALUATE ; odds ratio ; RISK-FACTOR ; B-CELL ; case control ; CELL LYMPHOMAS ; Epstein Barr virus ; LATENT INFECTION ; MONONUCLEOSIS
    Abstract: Epstein-Barr Virus (EBV) is consistently associated with distinct lymphoproliferative malignancies and aberrant EBV antibody patterns are found in most EBV cancer patients. We evaluate the detection of an abnormal reactive serological pattern to EBV (ab_EBV) infection and the risk of lymphoma in a multicentric case-control study. Serum samples were collected at study entry from 1,085 incident lymphoma cases from Spain, France, Germany, Czech Republic, Italy and 1,153 age, sex and country matched controls. EBV immunoglobulin G (IgG) serostatus was evaluated through a peptide-based ELISA combining immunodominant epitopes of EBNA1 (BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was performed to evaluate distinct antibody diversity patterns to EBV early antigens (EA), besides EBNA1, VCA-p18, VCA-p40 (BdRF1) and Zebra (BZLF1). Patients with chronic active EBV infection and aberrant EBV activity were characterized as having an abnormal reactive pattern (ab_EBV). Ab EBV was observed in 20.9% of 2,238 included subjects with an increased proportion of cases presenting ab_EBV as compared to the control population (23.9% vs. 18.0% p = 0.001). Ab_EBV positivity was a risk factor for all lymphomas combined (odds ratio [OR] = 1.42, 95% confidence interval [CI]=1.15-1.74), and specifically for chronic lymphocytic leukaemia (OR = 2.96, 95%CI = 2.22-3.95). Lower levels of ab EBV were observed for follicular lymphoma (OR = 0.38, 95%-CI = 0.15-0.98). EBV may be involved in a larger subset of lymphomas among clinically immunocompetent subjects than previously thought, probably explained by an underlying loss of immune control of EBV latent infection. Ab_EBV is a useful too] to explore EBV imbalances preceeding or paralleling possible EBV associated oncogenic events. (C) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17557295
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  • 3
    Keywords: CANCER ; CELLS ; neoplasms ; CT ; INFORMATION ; EPIDEMIOLOGY ; POPULATION ; RISK ; RISKS ; SAMPLE ; SAMPLES ; IDENTIFICATION ; LYMPHOMA ; HEALTH ; WOMEN ; hair dyes ; UNITED-STATES ; case-control studies ; non-Hodgkin lymphoma ; SUBTYPES ; USA ; N-ACETYLTRANSFERASE-1 ; non Hodgkin lymphoma ; non-Hodgkin ; CONSORTIUM ; N-ACETYLATION ; PHENYLENEDIAMINE
    Abstract: Personal use of hair dye has been inconsistently linked to risk of non-Hodgkin lymphoma (NHL), perhaps because of small samples or a lack of detailed information on personal hair-dye use in previous studies. This study included 4,461 NHL cases and 5,799 controls from the International Lymphoma Epidemiology Consortium 1988-2003. Increased risk of NHL (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.4) associated with hair-dye use was observed among women who began using hair dye before 1980. Analyses by NHL subtype showed increased risk for follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not for other NHL subtypes. The increased risks of FL (OR = 1.4, 95% CI: 1.1, 1.9) and CLL/SLL (OR = 1.5, 95% CI: 1.1, 2.0) were mainly observed among women who started using hair dyes before 1980. For women who began using hair dye in 1980 or afterward, increased FL risk was limited to users of dark-colored dyes (OR = 1.5, 95% CI: 1.1, 2.0). These results indicate that personal hair-dye use may play a role in risks of FL and CLL/SLL in women who started use before 1980 and that increased risk of FL among women who started use during or after 1980 cannot be excluded
    Type of Publication: Journal article published
    PubMed ID: 18408225
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  • 4
    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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