Citations 3
Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways
Kleinstern, Geffen , Yan, Huihuang , Berndt, Sonja I. , Ghesquières, Hervé , McKay, James , Wang, Sophia , Nieters, Alexandra, Ye, Yuanqing , Monnereau, Alain , Brooks‐Wilson, Angela , Lan, Qing , Melbye, Mads , Jackson, Rebecca D. , Purdue, Mark P. , Vajdic, Claire M. , Vermeulen, Roel , Cocco, Pier Luigi, Birmann, Brenda M. , Zeleniuch‐Jacquotte, Anne , Crouch, Simon , Sarangi, Vivekananda , Asmann, Yan W. , Offit, Kenneth , Salles, Gilles , Wu, Xifeng , Smedby, Karin E. , Skibola, Christine F., Rothman, Nathaniel , Cocco, Pierluigi , Asmann, Yan, Cocco, Pierluigi , Brooks-Wilson, Angela R , Vajdic, Claire M , Salles, Gilles A , Wang, Sophia S , Birmann, Brenda M , Zeleniuch-Jacquotte, Anne , Hildebrandt, Michelle A.T. , Vijai, Joseph , Teras, Lauren R. , Giles, Graham G. , Kraft, Peter , Albanes, Demetrius , Zhang, Yawei , Slager, Susan L. , Chanock, Stephen Jacob , Cerhan, James R.
Human Molecular Genetics | October 1, 2019 | Volume: 29 | Issue: 1 | Pages: 70-79
Abstract We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10−13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10−12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.
Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis
Kleinstern, Geffen , Camp, Nicola J. , Goldin, Lynn R. , Vachon, Celine M. , Vajdic, Claire M. , Sanjosé, Sílvia de, Weinberg, J. Brice , Benavente, Yolanda , Casabonne, Delphine, Liebow, Mark , Nieters, Alexandra, Hjalgrim, Henrik , Melbye, Mads , Glimelius, Bengt , Adami, Hans‐Olov , Brennan, Paul , McKay, James , Cocco, Pier Luigi, Call, Timothy G. , Hanson, Curtis A. , Robinson, Dennis P. , Chaffee, Kari G. , Brooks‐Wilson, Angela , Monnereau, Alain, Clavel, Jacqueline , Glenn, Martha, Curtin, Karen , Conde, Lucía , Bracci, Paige M. , Morton, Lindsay M. , Severson, Richard K., Chanock, Stephen J., Spinelli, John J., Johnston, James B. , Rothman, Nathaniel , Skibola, Christine F., Leis, José F., Smedby, Karin E. , Berndt, Sonja I. , Caporaso, Neil E., Rabe, Kari G. , Cocco, Pierluigi , Monnereau, Alain , Norman, Aaron D. , Hanson, Curtis, Robinson, Dennis, Cocco, Pierluigi , Brooks-Wilson, Angela R , Vajdic, Claire M , Morton, Lindsay M , Clavel, Jacqueline , Vachon, Celine M. , Casabonne, Delphine , Boffetta, Paolo , Maynadié, Marc , Shanafelt, Tait D. , Cozen, Wendy , Rothman, Nathaniel , Kay, Neil E. , Cerhan, James R. , Slager, Susan L.
Blood | April 19, 2018 | Volume: 131 | Issue: 23 | Pages: 2541-2551
Key Points PRS, based on the known CLL loci, predicts CLL risk with high discrimination. This PRS predicts risk of monoclonal B-cell lymphocytosis, a precursor to CLL and a condition that has clinical impact beyond risk for CLL.
Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph)
Wang, Sophia , Brennan, Paul , Holly, Elizabeth A., Sanjosé, Sílvia de, Cerhan, James R. , Spinelli, John J., Cocco, Pier Luigi, Mensah, Fiona , Nieters, Alexandra, Maso, Luigino Dal , Bracci, Paige M. , Costantini, Adele Seniori , Vineis, Paolo , Severson, Richard K., Roman, Eve , Weisenburger, Dennis D. , Franceschi, Silvia , Vecchia, Carlo La , Foretová, Lenka , Becker, Nikolaus, Staines, Anthony , Vornanen, Martine, Zheng, Tongzhang, Hartge, Patricia, Cocco, Pierluigi , Slager, Susan L. , Bernstein, Leslie , Boffetta, Paolo , Maynadié, Marc , Chiu, Brian C.‐H. , Zhang, Yawei , Cozen, Wendy , Davis, Scott , Cerhan, James R , Cocco, Pierluigi , Wang, Sophia S , Roman, Eve
Blood | December 22, 2006 | Volume: 109 | Issue: 8 | Pages: 3479-3488
AbstractA role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% CI = 1.1-2.3), and leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology.