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Genome-Wide Association Study of Classical Hodgkin Lymphoma and Epstein-Barr Virus Status-Defined Subgroups

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URAYAMA Kevin Y. JARRETT Ruth F. HJALGRIM Henrik DIEPSTRA Arjan KAMATANI Yoichiro CHABRIER Amelie GABORIEAU Valerie BOLAND Anne NIETERS Alexandra BECKER Nikolaus FORETOVÁ Lenka BENAVENTE Yolanda MAYNADIE Marc STAINES Anthony SHIELD Lesley LAKE Annette MONTGOMERY Dorothy TAYLOR Malcolm SMEDBY Karin Ekstrom AMINI Rose-Marie ADAMI Hans-Olov GLIMELIUS Bengt FEENSTRA Bjarke NOLTE Ilja M. VISSER Lydia VAN IMHOFF Gustaaf W. LIGHTFOOT Tracy COCCO Pierluigi KIEMENEY Lambertus VERMEULEN Sita H. HOLCATOVÁ Ivana VATTEN Lars MACFARLANE Gary J. THOMSON Peter CONWAY David I. BENHAMOU Simone AGUDO Antonio HEALY Claire M. OVERVAD Kim TJONNELAND Anne MELIN Beatrice CANZIAN Federico KHAW Kay-Tee TRAVIS Ruth C. PEETERS Petra H. M. GONZALEZ Carlos A. QUIROS Jose Ramon SANCHEZ Maria-Jose MARIA HUERTA Jose ARDANAZ Eva DORRONSORO Miren CLAVEL-CHAPELON Francoise BUENO-DE-MESQUITA H. Bas RIBOLI Elio ROMAN Eve BOFFETTA Paolo DE SANJOSE Silvia ZELENIKA Diana MELBYE Mads VAN DEN BERG Anke LATHROP Mark BRENNAN Paul MCKAY James D.

Rok publikování 2012
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of the National Cancer Institute
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Doi http://dx.doi.org/10.1093/jnci/djr516
Obor Onkologie a hematologie
Klíčová slova REED-STERNBERG CELLS; INFECTIOUS-MONONUCLEOSIS; SUSCEPTIBILITY LOCI; ENDOPLASMIC-RETICULUM; DISEASE HD; CLASS-I; RISK; GENES; POPULATION; PSORIASIS
Popis 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.

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