PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium.
Authors | Nieters A, Conde L, Slager SL, Brooks-Wilson A, Morton L, Skibola DR, Novak AJ, Riby J, Ansell SM, Halperin E, Shanafelt TD, Agana L, Wang AH, De Roos AJ, Severson RK, Cozen W, Spinelli J, Butterbach K, Becker N, de Sanjose S, Benavente Y, Cocco P, Staines A, MaynadiƩ M, Foretova L, Boffetta P, Brennan P, Lan Q, Zhang Y, Zheng T, Purdue M, Armstrong B, Kricker A, Vajdic CM, Grulich A, Smith MT, Bracci PM, Chanock SJ, Hartge P, Cerhan JR, Wang SS, Rothman N & Skibola CF. |
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Abstract | Many common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but individual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms (SNPs) within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5,633 B-cell NHL cases and 7,034 controls from eight InterLymph studies. rs3789068 in the pro-apoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (OR=1.21, p-random=2.21x10(-11)) with similar risk estimates for common B-cell subtypes. PRRC2A rs3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (OR=0.68, p-random=1.07x10(-9)) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes. |
Journal Name and Citation | Blood. 2012 Oct 9. [Epub ahead of print] |
Date of Publication | 2012/10/09 |
Publication Link | http://bloodjournal.hematologylibrary.org/content/early/2012/10/09/blood-2012-05-427989.long?hw-tma-check=true |