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

被引：12

作者：

Berndt, Sonja, I ^{[1
]}

Vijai, Joseph ^{[2
]}

Benavente, Yolanda ^{[3
,4
]}

Camp, Nicola J. ^{[5
,6
]}

Nieters, Alexandra ^{[7
]}

Wang, Zhaoming ^{[8
,9
]}

Smedby, Karin E. ^{[10
,11
]}

Kleinstern, Geffen ^{[12
]}

Hjalgrim, Henrik ^{[13
,14
,15
,16
]}

Besson, Caroline ^{[17
,18
]}

Skibola, Christine F. ^{[19
]}

Morton, Lindsay M. ^{[20
]}

Brooks-Wilson, Angela R. ^{[21
,22
]}

Teras, Lauren R. ^{[23
]}

Breeze, Charles ^{[20
]}

Arias, Joshua ^{[20
]}

Adami, Hans-Olov ^{[24
,25
,26
]}

Albanes, Demetrius ^{[20
]}

Anderson, Kenneth C. ^{[27
]}

Ansell, Stephen M. ^{[28
]}

Bassig, Bryan ^{[20
]}

Becker, Nikolaus ^{[29
]}

Bhatti, Parveen ^{[30
]}

Birmann, Brenda M. ^{[31
]}

Boffetta, Paolo ^{[32
,33
]}

Bracci, Paige M. ^{[34
]}

Brennan, Paul ^{[35
]}

Brown, Elizabeth E. ^{[36
]}

Burdett, Laurie ^{[37
]}

Cannon-Albright, Lisa A. ^{[5
,6
,38
]}

Chang, Ellen T. ^{[34
,39
]}

Chiu, Brian C. H. ^{[40
]}

Chung, Charles C. ^{[20
]}

Clavel, Jacqueline ^{[41
,42
]}

Cocco, Pierluigi ^{[43
]}

Colditz, Graham ^{[44
]}

Conde, Lucia ^{[45
]}

Conti, David, V ^{[46
]}

Cox, David G. ^{[47
]}

Curtin, Karen ^{[5
,6
]}

Casabonne, Delphine ^{[3
,4
]}

De Vivo, Immaculata ^{[25
,31
]}

Diver, W. Ryan ^{[23
]}

Dogan, Ahmet ^{[48
]}

Edlund, Christopher K. ^{[46
]}

Foretova, Lenka ^{[49
]}

Fraumeni, Joseph F., Jr. ^{[20
]}

Gabbas, Attilio ^{[50
]}

Ghesquieres, Herve ^{[51
,52
]}

Giles, Graham G. ^{[53
,54
,55
]}

机构：

[1] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[3] Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Programme, Barcelona, Spain

[4] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain

[5] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA

[6] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA

[7] Univ Med Ctr Freiburg, Inst Immunodeficiency, Freiburg, Germany

[8] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St, Memphis, TN 38105 USA

[9] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[10] Karolinska Inst, Dept Med, Stockholm, Sweden

[11] Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden

[12] Univ Haifa, Sch Publ Hlth, Haifa, Israel

[13] Statens Serum Inst, Dept Epidemiol Res, Div Hlth Surveillance & Res, Copenhagen, Denmark

[14] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark

[15] Rigshosp, Dept Haematol, Copenhagen, Denmark

[16] Danish Canc Soc, Danish Canc Soc Res Ctr, Copenhagen, Denmark

[17] Ctr Hosp Versailles, Le Chesnay, France

[18] Univ Paris Saclay, UVSQ, INSERM, Equipe Exposome & Heredite,CESP, Villejuif, France

[19] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA USA

[20] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada

[21] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada

[22] Amer Canc Soc, Dept Populat Sci, Atlanta, GA 30329 USA

[23] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[24] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[25] Univ Oslo, Inst Hlth & Soc, Clin Effectiveness Res Grp, Oslo, Norway

[26] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[27] Mayo Clin, Dept Internal Med, Rochester, MN USA

[28] German Canc Res Ctr, Div Canc Epidemiol, Baden-W Rttemberg, Heidelberg, Germany

[29] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA

[30] Brigham & Womens Hosp & Harvard Med Sch, Dept Med, Channing Div Network Med, Boston, MA USA

[31] SUNY Stony Brook, Stony Brook Canc Ctr, Stony Brook, NY 11794 USA

[32] Univ Bologna, Dept Med & Surg Sci, I-41026 Bologna, Italy

[33] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA

[34] Int Agcy Res Canc IARC, Lyon, France

[35] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA

[36] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Gaithersburg, MA USA

[37] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA

[38] Exponent Inc, Ctr Hlth Sci, Menlo Pk, CA USA

[39] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL USA

[40] INSERM, UMR1153, CRESS, Villejuif, France

[41] Univ Paris Cite, Villejuif, France

[42] Univ Manchester, Ctr Occupat & Environm Hlth, Div Populat Sci Hlth Serv Res & Primary Care, Manchester, Lancs, England

[43] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA

[44] UCL, Bill Lyons Informat Ctr, UCL Canc Inst, London, England

[45] Univ Southern Calif, USC Keck Sch Med, Dept Populat & Publ Hlth Sci, Los Angeles, CA USA

[46] Ctr Leon Berard, Canc Res Ctr Lyon, INSERM U1052, Lyon, France

[47] Mem Sloan Kettering Canc Ctr, Dept Lab Med, 1275 York Ave, New York, NY 10021 USA

[48] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic

[49] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy

[50] Lyon Sud Hosp, Hosp Civils Lyon, Dept Hematol, Pierre Benite, France

来源：

LEUKEMIA | 2022年 / 36卷 / 12期

关键词：

GENOME-WIDE ASSOCIATION; B-CELL; FOLLICULAR LYMPHOMA; RISK; LOCI; LEUKEMIA; CLASSIFICATION; CANCER; HHEX; METAANALYSIS;

D O I：

10.1038/s41375-022-01711-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 x 10(-8)) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 x 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 x 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.

引用

页码：2835 / 2844

页数：10

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