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

Authors	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 FORETOVÁ 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.
Year of publication	2012
Type	Article in Periodical
Magazine / Source	Blood
MU Faculty or unit	Faculty of Medicine
Citation
Doi	http://dx.doi.org/10.1182/blood-2012-05-427989
Field	Oncology and hematology
Keywords	GENOME-WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; FOLLICULAR LYMPHOMA; GERMLINE VARIATION; SUSCEPTIBILITY; TNF; POLYMORPHISMS; NEOPLASMS; APOPTOSIS; LEUKEMIA
Description	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. (Blood. 2012; 120(23):4645-4648)