GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.
PLoS Genet
; 7(4): e1001378, 2011 Apr.
Article
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| MEDLINE
| ID: mdl-21533074
ABSTRACT
Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined)â = 0.64, P(combined)â = 2 × 10(-21)) located 962 bp away from rs10484561 (r(2)<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012OR(adjusted) â= 0.70, P(adjusted)â =â 4 × 10(-12); rs10484561OR(adjusted) â= 1.64, P(adjusted) â= 5 × 10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined) â= 1.36, P(combined)â =â 1.4 × 10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cromosomas Humanos Par 6
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Antígenos de Histocompatibilidad Clase II
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Linfoma Folicular
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Linfoma de Células B Grandes Difuso
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Predisposición Genética a la Enfermedad
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suecia