PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: Results from the InterLymph consortium

Alexandra Nieters*, Lucia Conde, Susan L. Slager, Angela Brooks-Wilson, Lindsay Morton, Danica R. Skibola, Anne J. Novak, Jacques Riby, Stephen M. Ansell, Eran Halperin, Tait D. Shanafelt, Luz Agana, Alice H. Wang, Anneclaire J. De Roos, Richard K. Severson, Wendy Cozen, John Spinelli, Katja Butterbach, Nikolaus Becker, Silvia De SanjoseYolanda Benavente, Pierluigi Cocco, Anthony Staines, Marc Maynadié, Lenka Foretova, Paolo Boffetta, Paul Brennan, Qing Lan, Yawei Zhang, Tongzhang Zheng, Mark Purdue, Bruce Armstrong, Anne Kricker, Claire M. Vajdic, Andrew Grulich, Martyn T. Smith, Paige M. Bracci, Stephen J. Chanock, Patricia Hartge, James R. Cerhan, Sophia S. Wang, Nathaniel Rothman, Christine F. Skibola

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 within InterLymph, a large international consortium of NHL case-control studies.Ameta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 Inter-Lymph studies. rs3789068 in the proapoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (odds ratio = 1.21, P random = 2.21 × 10-11), 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 (odds ratio = 0.68, P random = 1.07 × 10 -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.

Original languageEnglish
Pages (from-to)4645-44648
Number of pages40004
JournalBlood
Volume120
Issue number23
DOIs
StatePublished - 29 Nov 2012

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