B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS

Sophia S Wang; Claire M Vajdic; Martha S Linet; Susan L Slager; Jenna Voutsinas; Alexandra Nieters; Delphine Casabonne; James R Cerhan; Wendy Cozen; Graciela Alarcón; Otoniel Martínez-Maza; Elizabeth E Brown; Paige M Bracci; Jennifer Turner; Henrik Hjalgrim; Parveen Bhatti; Yawei Zhang; Brenda M Birmann; Christopher R Flowers; Ora Paltiel; Elizabeth A Holly; Eleanor Kane; Dennis D Weisenburger; Marc Maynadié; Pierluigi Cocco; Lenka Foretova; Elizabeth Crabb Breen; Qing Lan; Angela Brooks-Wilson; Anneclaire J De Roos; Martyn T Smith; Eve Roman; Paolo Boffetta; Anne Kricker; Tongzhang Zheng; Christine F Skibola; Jacqueline Clavel; Alain Monnereau; Stephen J Chanock; Nathaniel Rothman; Yolanda Benavente; Patricia Hartge; Karin E Smedby

doi:10.1158/1055-9965.EPI-21-0875

B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS

Cancer Epidemiol Biomarkers Prev. 2022 May 4;31(5):1103-1110. doi: 10.1158/1055-9965.EPI-21-0875.

Authors

Sophia S Wang¹, Claire M Vajdic², Martha S Linet³, Susan L Slager⁴, Jenna Voutsinas¹, Alexandra Nieters⁵, Delphine Casabonne^{6

7}, James R Cerhan⁴, Wendy Cozen⁸, Graciela Alarcón⁹, Otoniel Martínez-Maza^{10

11

12}, Elizabeth E Brown^{13

14}, Paige M Bracci¹⁵, Jennifer Turner^{16

17}, Henrik Hjalgrim¹⁸, Parveen Bhatti¹⁹, Yawei Zhang²⁰, Brenda M Birmann²¹, Christopher R Flowers²², Ora Paltiel²³, Elizabeth A Holly¹⁵, Eleanor Kane²⁴, Dennis D Weisenburger²⁵, Marc Maynadié²⁶, Pierluigi Cocco²⁷, Lenka Foretova²⁸, Elizabeth Crabb Breen²⁹, Qing Lan³, Angela Brooks-Wilson³⁰, Anneclaire J De Roos³¹, Martyn T Smith³², Eve Roman²⁴, Paolo Boffetta^{33

34}, Anne Kricker³⁵, Tongzhang Zheng³⁶, Christine F Skibola²², Jacqueline Clavel³⁷, Alain Monnereau^{37

38}, Stephen J Chanock³, Nathaniel Rothman³, Yolanda Benavente^{6

7}, Patricia Hartge³, Karin E Smedby³⁹

Affiliations

¹ Division of Health Analytics, Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Monrovia, California.
² Centre for Big Data Research in Health, The University of New South Wales, Sydney, New South Wales, Australia.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
⁴ Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
⁵ The Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany.
⁶ Unit of Infections and Cancer, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program - Epibell, IDIBELL, Institut Català d' Oncologia/IDIBELL, Barcelona, Spain.
⁷ The Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), Madrid, Spain.
⁸ Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, California.
⁹ Division of Clinical Immunology and Rheumatology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
¹⁰ Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
¹¹ Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
¹² Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California.
¹³ Department of Pathology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
¹⁴ O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, Alabama.
¹⁵ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
¹⁶ Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia.
¹⁷ Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
¹⁸ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
¹⁹ British Columbia Cancer Research Center, Vancouver, British Columbia, Canada.
²⁰ Department of Cancer Prevention and Control at the National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
²¹ Channing Division of Network Medicine, Department of Medicine Research, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
²² Winship Cancer Institute, Emory University, Atlanta, Georgia.
²³ Department of Hematology, The Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Hadassah University Medical Center, Jerusalem, Israel.
²⁴ Department of Health Sciences, University of York, York, United Kingdom.
²⁵ Department of Pathology, City of Hope, Duarte, California.
²⁶ Registry of Hematological Malignancies of Cote d'Or, INSERM U1231, Burgundy University and University Hospital, Dijon, France (Maynadie).
²⁷ Occupational Health Section, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
²⁸ Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
²⁹ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
³⁰ Department of Biomedical Physiology and Kinesiology, Faculty of Science, Simon Fraser University, Vancouver, British Columbia, Canada.
³¹ Department of Environmental and Occupational Health, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania.
³² Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California.
³³ Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York.
³⁴ Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
³⁵ Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.
³⁶ Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island.
³⁷ Centre of Research in Epidemiology and Statistics (CRESS), UMR1153, INSERM, Université de Paris, Paris, France.
³⁸ Registre des Hémopathies Malignes de la Gironde, Institut Bergonié, University of Bordeaux, Inserm, Team EPICENE, UMR 1219, Paris, France.
³⁹ Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Background: A previous International Lymphoma Epidemiology (InterLymph) Consortium evaluation of joint associations between five immune gene variants and autoimmune conditions reported interactions between B-cell response-mediated autoimmune conditions and the rs1800629 genotype on risk of B-cell non-Hodgkin lymphoma (NHL) subtypes. Here, we extend that evaluation using NHL subtype-specific polygenic risk scores (PRS) constructed from loci identified in genome-wide association studies of three common B-cell NHL subtypes.

Methods: In a pooled analysis of NHL cases and controls of Caucasian descent from 14 participating InterLymph studies, we evaluated joint associations between B-cell-mediated autoimmune conditions and tertile (T) of PRS for risk of diffuse large B-cell lymphoma (DLBCL; n = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression.

Results: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95% confidence interval (CI), 1.08-1.43; T3 vs. T1: OR = 1.81; 95% CI, 1.59-2.07; P-trend (Ptrend) < 0.0001]. DLBCL risk also increased with increasing PRS tertile among those with an autoimmune condition, being highest for those with a B-cell-mediated autoimmune condition and a T3 PRS [OR = 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend < 0.0001, P-interaction (Pinteraction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction.

Conclusions: Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions.

Impact: Targeted genetic (PRS) screening among population subsets with autoimmune conditions may offer opportunities for identifying those at highest risk for (and early detection from) DLBCL.

MeSH terms

Autoimmune Diseases* / epidemiology
Autoimmune Diseases* / genetics
B-Lymphocytes
Case-Control Studies
Genome-Wide Association Study
Humans
Lymphoma, Follicular* / epidemiology
Lymphoma, Follicular* / genetics
Lymphoma, Large B-Cell, Diffuse* / epidemiology
Lymphoma, Large B-Cell, Diffuse* / genetics

Abstract

MeSH terms

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