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 Sanjose; Yolanda 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

doi:10.1182/blood-2012-05-427989

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

Research output: Contribution to journal › Article › peer-review

22 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 language	English (US)
Pages (from-to)	4645-44648
Number of pages	40004
Journal	Blood
Volume	120
Issue number	23
DOIs	https://doi.org/10.1182/blood-2012-05-427989
State	Published - Nov 29 2012
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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10.1182/blood-2012-05-427989

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Nieters, A., Conde, L., Slager, S. L., Brooks-Wilson, A., Morton, L., Skibola, D. R., Novak, A. J., Riby, J., Ansell, S. M., Halperin, E., Shanafelt, T. D., Agana, L., Wang, A. H., De Roos, A. J., Severson, R. K., Cozen, W., Spinelli, J., Butterbach, K., Becker, N., ... Skibola, C. F. (2012). PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: Results from the InterLymph consortium. Blood, 120(23), 4645-44648. https://doi.org/10.1182/blood-2012-05-427989

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, Maynadié, 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 2012, 'PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: Results from the InterLymph consortium', Blood, vol. 120, no. 23, pp. 4645-44648. https://doi.org/10.1182/blood-2012-05-427989

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

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.",

author = "Alexandra Nieters and Lucia Conde and Slager, {Susan L.} and Angela Brooks-Wilson and Lindsay Morton and Skibola, {Danica R.} and Novak, {Anne J.} and Jacques Riby and Ansell, {Stephen M.} and Eran Halperin and Shanafelt, {Tait D.} and Luz Agana and Wang, {Alice H.} and {De Roos}, {Anneclaire J.} and Severson, {Richard K.} and Wendy Cozen and John Spinelli and Katja Butterbach and Nikolaus Becker and {De Sanjose}, Silvia and Yolanda Benavente and Pierluigi Cocco and Anthony Staines and Marc Maynadi{\'e} and Lenka Foretova and Paolo Boffetta and Paul Brennan and Qing Lan and Yawei Zhang and Tongzhang Zheng and Mark Purdue and Bruce Armstrong and Anne Kricker and Vajdic, {Claire M.} and Andrew Grulich and Smith, {Martyn T.} and Bracci, {Paige M.} and Chanock, {Stephen J.} and Patricia Hartge and Cerhan, {James R.} and Wang, {Sophia S.} and Nathaniel Rothman and Skibola, {Christine F.}",

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doi = "10.1182/blood-2012-05-427989",

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T1 - PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma

T2 - Results from the InterLymph consortium

AU - Nieters, Alexandra

AU - Conde, Lucia

AU - Slager, Susan L.

AU - Brooks-Wilson, Angela

AU - Morton, Lindsay

AU - Skibola, Danica R.

AU - Novak, Anne J.

AU - Riby, Jacques

AU - Ansell, Stephen M.

AU - Halperin, Eran

AU - Shanafelt, Tait D.

AU - Agana, Luz

AU - Wang, Alice H.

AU - De Roos, Anneclaire J.

AU - Severson, Richard K.

AU - Cozen, Wendy

AU - Spinelli, John

AU - Butterbach, Katja

AU - Becker, Nikolaus

AU - De Sanjose, Silvia

AU - Benavente, Yolanda

AU - Cocco, Pierluigi

AU - Staines, Anthony

AU - Maynadié, Marc

AU - Foretova, Lenka

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Lan, Qing

AU - Zhang, Yawei

AU - Zheng, Tongzhang

AU - Purdue, Mark

AU - Armstrong, Bruce

AU - Kricker, Anne

AU - Vajdic, Claire M.

AU - Grulich, Andrew

AU - Smith, Martyn T.

AU - Bracci, Paige M.

AU - Chanock, Stephen J.

AU - Hartge, Patricia

AU - Cerhan, James R.

AU - Wang, Sophia S.

AU - Rothman, Nathaniel

AU - Skibola, Christine F.

PY - 2012/11/29

Y1 - 2012/11/29

N2 - 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.

AB - 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.

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

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