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American Society of Hematology, Blood, 23(120), p. 4645-4648, 2012

DOI: 10.1182/blood-2012-05-427989

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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Nieters, Alexandra Conde, Lucia Slager, Susan L Brooks-Wilson, Angela Morton, Lindsay Skibola, Danica R Novak, Anne J Riby, Jacques Ansell, Stephen M Halperin, Eran Shanafelt, Tait D Agana, Luz Wang, Alice H De Roos, Anneclaire J Severson, Richard K Cozen, Wendy Spinelli, John Butterbach, Katja Becker, Nikolaus de Sanjose, Silvia Benavente, Yolanda Cocco, Pierluigi Staines, Anthony Maynadie, Marc Foretova, Lenka Boffetta, Paolo Brennan, Paul Lan, Qing Zhang, Yawei Zheng, Tongzhang Purdue, Mark Armstrong, Bruce Kricker, Anne Vajdic, Claire M Grulich, Andrew Smith, Martyn T Bracci, Paige M Chanock, Stephen J Hartge, Patricia Cerhan, James R Wang, Sophia S Rothman, Nathaniel Skibola, Christine F eng CA104682/CA/NCI NIH HHS/ CA122663/CA/NCI NIH HHS/ CA154643-01A1/CA/NCI NIH HHS/ CA45614/CA/NCI NIH HHS/ CA62006/CA/NCI NIH HHS/ CA89745/CA/NCI NIH HHS/ CA92153/CA/NCI NIH HHS/ UL1 TR000142/TR/NCATS NIH HHS/ Canadian Institutes of Health Research/Canada Multicenter Study Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't 2012/10/11 06:00 Blood. 2012 Nov 29;120(23):4645-8. doi: 10.1182/blood-2012-05-427989. Epub 2012 Oct 9. ; International audience ; 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. A meta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 InterLymph 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 x 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 x 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.