Bryan A Bassig1, James R Cerhan2, Wing-Yan Au3, Hee Nam Kim4,5, Suleeporn Sangrajrang6, Wei Hu1, Jovic Tse3, Sonja Berndt1, Tongzhang Zheng7, Heping Zhang7, Pattarapong Pornsopone8, Je-Jung Lee9, Hyeoung-Joon Kim4,9, Christine F Skibola10, Joseph Vijai11, Laurie Burdette1,12, Meredith Yeager1,12, Paul Brennan13, Min-Ho Shin5,14, Raymond Liang3, Stephen Chanock1, Qing Lan1, Nathaniel Rothman1. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA. 2. Division of Epidemiology, Mayo Clinic, Rochester, MN, USA. 3. Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China. 4. Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, South Korea. 5. Center for Creative Biomedical Scientists, Chonnam National University, Gwangju, South Korea. 6. Research Division, National Cancer Institute, Bangkok, Thailand. 7. Yale University School of Public Health, New Haven, CT, USA. 8. Medical Oncology Department, National Cancer Institute, Bangkok, Thailand. 9. Department of Hematology/Oncology, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, South Korea. 10. Department of Epidemiology, The University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA. 11. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 12. Cancer Genomics Research Laboratory, National Cancer Institute, NIH, DHHS, Gaithersburg, MD, USA. 13. Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France. 14. Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea.
Abstract
OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL) and is the most common NHL subtype diagnosed worldwide. The first large-scale genome-wide association study (GWAS) of DLBCL with over 4000 cases conducted among individuals of European ancestry recently identified five independent SNPs that achieved genome-wide significance, and two SNPs that showed a suggestive association with DLBCL risk. METHODS: To evaluate whether Eastern Asians and individuals of European ancestry share similar genetic risk factors for this disease, we attempted to replicate these GWAS findings in a pooled series of 1124 DLBCL cases and 3596 controls from Hong Kong, South Korea, and Thailand. RESULTS: Three of the five genome-wide significant SNPs from the DLBCL GWAS were significantly associated with DLBCL in our study population, including the top finding from the GWAS, EXOC2 rs116446171, which achieved genome-wide significance in our data (per allele OR = 2.04, 95% CI = 1.63-2.56; ptrend = 3.9 × 10(-10)). Additionally, we observed a significant association with PVT1 rs13255292 (per allele OR = 1.34, 95% CI = 1.19-1.52; ptrend = 2.1 × 10(-6)), which was the second strongest finding in the GWAS, and with HLA-B rs2523607 (per allele OR = 3.05, 95% CI = 1.32-7.05; ptrend = 0.009). CONCLUSIONS: Our study, which provides the first evaluation in Eastern Asians of SNPs definitively associated with DLBCL risk in individuals of European ancestry, indicates that at least some of the genetic factors associated with risk of DLBCL are similar between these populations.
OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL) and is the most common NHL subtype diagnosed worldwide. The first large-scale genome-wide association study (GWAS) of DLBCL with over 4000 cases conducted among individuals of European ancestry recently identified five independent SNPs that achieved genome-wide significance, and two SNPs that showed a suggestive association with DLBCL risk. METHODS: To evaluate whether Eastern Asians and individuals of European ancestry share similar genetic risk factors for this disease, we attempted to replicate these GWAS findings in a pooled series of 1124 DLBCL cases and 3596 controls from Hong Kong, South Korea, and Thailand. RESULTS: Three of the five genome-wide significant SNPs from the DLBCL GWAS were significantly associated with DLBCL in our study population, including the top finding from the GWAS, EXOC2rs116446171, which achieved genome-wide significance in our data (per allele OR = 2.04, 95% CI = 1.63-2.56; ptrend = 3.9 × 10(-10)). Additionally, we observed a significant association with PVT1rs13255292 (per allele OR = 1.34, 95% CI = 1.19-1.52; ptrend = 2.1 × 10(-6)), which was the second strongest finding in the GWAS, and with HLA-Brs2523607 (per allele OR = 3.05, 95% CI = 1.32-7.05; ptrend = 0.009). CONCLUSIONS: Our study, which provides the first evaluation in Eastern Asians of SNPs definitively associated with DLBCL risk in individuals of European ancestry, indicates that at least some of the genetic factors associated with risk of DLBCL are similar between these populations.
Authors: Geffen Kleinstern; Huihuang Yan; Michelle A T Hildebrandt; Joseph Vijai; Sonja I Berndt; Hervé Ghesquières; James McKay; Sophia S Wang; Alexandra Nieters; Yuanqing Ye; Alain Monnereau; Angela R Brooks-Wilson; Qing Lan; Mads Melbye; Rebecca D Jackson; Lauren R Teras; Mark P Purdue; Claire M Vajdic; Roel C H Vermeulen; Graham G Giles; Pier Luigi Cocco; Brenda M Birmann; Peter Kraft; Demetrius Albanes; Anne Zeleniuch-Jacquotte; Simon Crouch; Yawei Zhang; Vivekananda Sarangi; Yan Asmann; Kenneth Offit; Gilles Salles; Xifeng Wu; Karin E Smedby; Christine F Skibola; Susan L Slager; Nathaniel Rothman; Stephen J Chanock; James R Cerhan Journal: Hum Mol Genet Date: 2020-01-01 Impact factor: 6.150
Authors: Jean L Koff; Dai Chihara; Anh Phan; Loretta J Nastoupil; Jessica N Williams; Christopher R Flowers Journal: Curr Hematol Malig Rep Date: 2015-09 Impact factor: 3.952
Authors: Charlie Zhong; Loren Gragert; Martin Maiers; Brian T Hill; Jean Garcia-Gomez; Ketevan Gendzekhadze; David Senitzer; Joo Song; Dennis Weisenburger; Leanne Goldstein; Sophia S Wang Journal: Leuk Lymphoma Date: 2019-06-19
Authors: Michelle J Lee; Jean L Koff; Jeffrey M Switchenko; C Ileen Jhaney; R Andrew Harkins; Sharvil P Patel; Sandeep S Dave; Christopher R Flowers Journal: Cancer Date: 2020-05-29 Impact factor: 6.860
Authors: Shehnaz K Hussain; Solomon B Makgoeng; Matthew J Everly; Marc T Goodman; Otoniel Martínez-Maza; Lindsay M Morton; Christina A Clarke; Charles F Lynch; Jon Snyder; Ajay Israni; Bertram L Kasiske; Eric A Engels Journal: Transplantation Date: 2016-11 Impact factor: 5.385
Authors: Jeffrey M Switchenko; Catherine Bulka; Kevin Ward; Jean L Koff; A Rana Bayakly; P Barry Ryan; Lance A Waller; Christopher R Flowers Journal: Cancer Epidemiol Date: 2016-03-02 Impact factor: 2.984
Authors: M D Mathias; M V Ortiz; H Magnan; S R Ambati; E K Slotkin; A J Chou; M F Walsh; K Offit; C Moskowitz; A Kentsis; L H Wexler Journal: Biomark Res Date: 2017-02-08
Authors: Mary L McMaster; Sonja I Berndt; Jianqing Zhang; Susan L Slager; Shengchao Alfred Li; Claire M Vajdic; Karin E Smedby; Huihuang Yan; Brenda M Birmann; Elizabeth E Brown; Alex Smith; Geffen Kleinstern; Mervin M Fansler; Christine Mayr; Bin Zhu; Charles C Chung; Ju-Hyun Park; Laurie Burdette; Belynda D Hicks; Amy Hutchinson; Lauren R Teras; Hans-Olov Adami; Paige M Bracci; James McKay; Alain Monnereau; Brian K Link; Roel C H Vermeulen; Stephen M Ansell; Ann Maria; W Ryan Diver; Mads Melbye; Akinyemi I Ojesina; Peter Kraft; Paolo Boffetta; Jacqueline Clavel; Edward Giovannucci; Caroline M Besson; Federico Canzian; Ruth C Travis; Paolo Vineis; Elisabete Weiderpass; Rebecca Montalvan; Zhaoming Wang; Meredith Yeager; Nikolaus Becker; Yolanda Benavente; Paul Brennan; Lenka Foretova; Marc Maynadie; Alexandra Nieters; Silvia de Sanjose; Anthony Staines; Lucia Conde; Jacques Riby; Bengt Glimelius; Henrik Hjalgrim; Nisha Pradhan; Andrew L Feldman; Anne J Novak; Charles Lawrence; Bryan A Bassig; Qing Lan; Tongzhang Zheng; Kari E North; Lesley F Tinker; Wendy Cozen; Richard K Severson; Jonathan N Hofmann; Yawei Zhang; Rebecca D Jackson; Lindsay M Morton; Mark P Purdue; Nilanjan Chatterjee; Kenneth Offit; James R Cerhan; Stephen J Chanock; Nathaniel Rothman; Joseph Vijai; Lynn R Goldin; Christine F Skibola; Neil E Caporaso Journal: Nat Commun Date: 2018-10-10 Impact factor: 14.919