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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

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  • 06/25/2025
Type of Material
Authors
    Sonja I Berndt, National Cancer Institute, BethesdaJoseph Vijai, Memorial Sloan Kettering Cancer Center, New YorkYolanda Benavente, atalan Institute of Oncology-IDIBELL, L’Hospitalet de LlobregatNicola J Camp, University of UtahAlexandra Nieters, University Medical Center FreiburgZhaoming Wang, St. Jude Children’s Research Hospital, MemphisKarin E Smedby, Karolinska Institutet, StockholmGeffen Kleinstern, University of HaifaHenrik Hjalgrim, University of CopenhagenCaroline Besson, Centre Hospitalier de Versailles, Le Chesnay, FranceChristine F Skibola, Emory UniversityLindsay M Morton, National Cancer Institute, BethesdaAngela R Brooks-Wilson, Simon Fraser UniversityLauren R Teras, American Cancer Society, AtlantaCharles Breeze, National Cancer Institute, BethesdaJoshua Arias, National Cancer Institute, BethesdaHans-Olov Adami, University of OsloDemetrius Albanes, National Cancer Institute, BethesdaKenneth C Anderson, Harvard Medical SchoolStephen M Ansell, Mayo Clinic, RochesterBryan Bassig, National Cancer Institute, BethesdaNikolaus Becker, German Cancer Research Center (DKFZ), HeidelbergParveen Bhatti, Fred Hutchinson Cancer Research Center, SeattleBrenda M Birmann, Harvard Medical SchoolPaolo Boffetta, Stony Brook UniversityPaige M Bracci, University of CaliforniaPaul Brennan, International Agency for Research on Cancer (IARC), LyonElizabeth E Brown, University of AlabamaLaurie Burdett, National Cancer Institute, GaithersburgLisa A Cannon-Albright, University of UtahEllen T Chang, University of California San FranciscoBrian C H Chiu, University of ChicagoCharles C Chung, National Cancer Institute, BethesdaJacqueline Clavel, Université de Paris-Cité, VillejuifPierluigi Cocco, University of ManchesterGraham Colditz, Washington UniversityLucia Conde, University College LondonDavid V Conti, University of Southern CaliforniaDavid G Cox, Cancer Research Center of Lyon, Centre Léon BérardKaren Curtin, University of UtahDelphine Casabonne, Catalan Inst Oncol IDIBELLImmaculata De Vivo, Harvard Medical SchoolArjan Diepstra, University of GroningenW Ryan Diver, American Cancer Society, AtlantaAhmet Dogan, Memorial Sloan Kettering Cancer Center, New YorkChristopher K Edlund, University of Southern CaliforniaLenka Foretova, Masaryk Memorial Cancer Institute, BrnoJoseph F Fraumeni, Jr, National Cancer Institute, BethesdaAttilio Gabbas, University of CagliariHervé Ghesquieres, Hospices Civils de Lyon, Lyon Sud HospitalGraham G Giles, University of MelbourneSally Glaser, Stanford Cancer Institute, CaliforniaMartha Glenn, University of UtahBengt Glimelius, Uppsala UniversityJian Gu, MD Anderson Cancer Center, HoustonThomas M Habermann, Mayo Clinic, RochesterChristopher A Haiman, University of Southern CaliforniaCorinne Haioun, University Paris Est, CréteilJonathan N Hofmann, National Cancer Institute, BethesdaTheodore R Holford, Yale School of Public Health, New HavenElizabeth A Holly, University of CaliforniaAmy Hutchinson, National Cancer Institute, GaithersburgAalin Izhar, Memorial Sloan Kettering Cancer CenterRebecca D Jackson, Ohio State UniversityRuth F Jarrett, MRC-University, Glasgow, United Kingdom.Rudolph Kaaks, German Cancer Research Center (DKFZ), HeidelbergEleanor Kane, University of YorkLaurence N Kolonel, University of HawaiiYinfei Kong, California State UniversityPeter Kraft, Harvard T.H. Chan School of Public Health, BostonAnne Kricker, University of SydneyAnnette Lake, MRC-University of GlasgowQing Lan, National Cancer Institute, BethesdaCharles Lawrence, Westat, Rockville, MarylandDalin Li, Immunobiology Research Institute, Cedars-Sinai Medical Center, Los AngelesMark Liebow, Mayo Clinic, RochesterBrian K Link, University of IowaCorrado Magnani, University of Piemonte OrientaleMarc Maynadie, Dijon University Hospital, Dijon, FranceJames McKay, International Agency for Research on Cancer (IARC), LyonMads Melbye, University of CopenhagenLucia Miligi, ancer Prevention and Research Institute (ISPO), FlorenceRoger L Milne, University of MelbourneThierry J Molina, Université Paris Cité, Institut Imagine, FranceAlain Monnereau, Institut Bergonié, Bordeaux Cedex, FranceRebecca Montalvan, Westat, Rockville, MarylandKari E North, University of North CarolinaAnne J Novak, Mayo Clinic, RochesterKenan Onel, Hofstra/Northwell, Hempstead, New YorkMark P Purdue, National Cancer Institute, BethesdaKristin A Rand, University of Southern CaliforniaElio Riboli, Imperial College LondonJacques Riby, University of AlabamaEve Roman, University of YorkGilles Salles, Memorial Sloan Kettering Cancer CenterDouglas W Sborov, University of UtahRichard K Severson, Wayne State University, DetroitTait D Shanafelt, Stanford UniversityMartyn T Smith, University of California, BerkeleyAlexandra Smith, University of YorkKevin W Song, University of British ColumbiaLei Song, National Cancer Institute, FrederickMelissa C Southey, Monash University, ClaytonJohn J Spinelli, University of British ColumbiaAnthony Staines, Dublin City UniversityDeborah Stephens, University of UtahHeather J Sutherland, University of British ColumbiaKaitlyn Tkachuk, Memorial Sloan Kettering Cancer Center, New YorkCarrie A Thompson, Mayo Clinic, RochesterHervé Tilly, Université de Rouen, FranceLesley F Tinker, Fred Hutchinson Cancer Research Center, SeattleRuth C Travis, University of OxfordJenny Turner, Macquarie University, SydneyCeline M Vachon, Mayo Clinic, Rochester, MinnesotaClaire M Vajdic, Mayo Clinic, Rochester, MinnesotaAnke Van den Berg, University of GroningenDavid J Van den Berg, University of Southern CaliforniaRoel C H Vermeulen, Univ Med Ctr UtrechtPaolo Vineis, Human Genetics Foundation, Turin, ItalySophia S Wang, ity of Hope Beckman Research Institute, DuarteElisabete Weiderpass, International Agency for Research on Cancer (IARC), LyonGeorge J Weiner, University of IowaStephanie Weinstein, National Cancer Institute, BethesdaNicole Wong Doo, University of SydneyYuanqing Ye, MD Anderson Cancer Center, HoustonMeredith Yeager, National Cancer Institute, BethesdaKai Yu, National Cancer Institute, BethesdaAnne Zeleniuch-Jacquotte, New York UniversityYawei Zhang, ale School of Public Health, New HavenTongzhang Zheng, Brown UniversityElad Ziv, University of California, San FranciscoJoshua Sampson, National Cancer Institute, BethesdaNilanjan Chatterjee, National Cancer Institute, BethesdaKenneth Offit, Memorial Sloan Kettering Cancer Center, New YorkWendy Cozen, University of CaliforniaXifeng Wu, MD Anderson Cancer Center, HoustonJames R Cerhan, Mayo Clinic, RochesterStephen J Chanock, National Cancer Institute, BethesdaSusan L Slager, Mayo Clinic, RochesterNathaniel Rothman, National Cancer Institute, Bethesda
Language
  • English
Date
  • 2022-10-22
Publisher
  • SPRINGERNATURE
Publication Version
Copyright Statement
  • © 2024 Springer Nature Limited
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 36
Issue
  • 12
Start Page
  • 2835
End Page
  • 2844
Grant/Funding Information
  • This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH
Supplemental Material (URL)
Abstract
  • Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
Author Notes
  • Sonja Berndt, Pharm.D., Ph.D. Senior Investigator, National Cancer Institute, Division of Cancer Epidemiology & Genetics, 9609 Medical Center Drive, Room 6E610, MSC 9771, Bethesda, MD 20892, berndts@mail.nih.gov
Keywords
Research Categories
  • Health Sciences, Oncology
  • Biology, Genetics
  • Health Sciences, Epidemiology
  • Health Sciences, Medicine and Surgery

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