Infectious mononucleosis, immune genotypes, and non-Hodgkin lymphoma (NHL): an InterLymph Consortium study

Niquelle Brown Wadé; Cindy M Chang; David Conti; Joshua Millstein; Christine Skibola; Alexandra Nieters; Sophia S Wang; Silvia De Sanjose; Eleanor Kane; John J Spinelli; Paige Bracci; Yawei Zhang; Susan Slager; Jun Wang; Henrik Hjalgrim; Karin Ekstrom Smedby; Elizabeth E Brown; Ruth F Jarrett; Wendy Cozen; InterLymph Consortium Immunology and Infection Working Group

doi:10.1007/s10552-020-01266-4

Infectious mononucleosis, immune genotypes, and non-Hodgkin lymphoma (NHL): an InterLymph Consortium study

Cancer Causes Control. 2020 May;31(5):451-462. doi: 10.1007/s10552-020-01266-4. Epub 2020 Mar 2.

Authors

Niquelle Brown Wadé^{1

2}, Cindy M Chang³, David Conti^{1

4}, Joshua Millstein^{1

4}, Christine Skibola⁵, Alexandra Nieters⁶, Sophia S Wang⁷, Silvia De Sanjose^{8

9}, Eleanor Kane¹⁰, John J Spinelli^{11

12}, Paige Bracci¹³, Yawei Zhang¹⁴, Susan Slager¹⁵, Jun Wang^{1

4}, Henrik Hjalgrim^{16

17}, Karin Ekstrom Smedby¹⁸, Elizabeth E Brown¹⁹, Ruth F Jarrett²⁰, Wendy Cozen^{21

22

23}; InterLymph Consortium Immunology and Infection Working Group

Affiliations

¹ Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
² Cigna Health and Life Insurance Company (Cigna), Bloomfield, CT, USA.
³ Division of Population Health Sciences, Center for Tobacco Products, Food and Drug Administration, Bethesda, MD, USA.
⁴ USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁵ Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
⁶ Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, University of Freiburg, Freiburg, Germany.
⁷ Department of Computational and Quantitative Medicine, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
⁸ Sexual and Reproductive Health, PATH, Seattle, WA, USA.
⁹ Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
¹⁰ Department of Health Sciences, University of York, York, YO10 5DD, UK.
¹¹ Population Oncology, BC Cancer Agency, Vancouver, Canada.
¹² School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
¹³ Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA.
¹⁴ Department of Surgery, Yale School of Medicine and Yale School of Public Health, New Haven, CT, USA.
¹⁵ Department of Epidemiology, Mayo Clinic, Rochester, MN, USA.
¹⁶ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
¹⁷ Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
¹⁸ Karolinska Institutet, Sweden University Hospital, Karolinska University, Stockholm, Sweden.
¹⁹ Department of Pathology, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
²⁰ MRC-University of Glasgow Centre for Virus Research, Glasgow, Scotland.
²¹ Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [email protected].
²² USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [email protected].
²³ Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. [email protected].

Abstract

Purpose: We explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case-control analysis.

Methods: A total of 7,926 NHL patients and 10,018 controls from 12 case-control studies were included. Studies were conducted during various time periods between 1988 and 2008, and participants were 17-96 years of age at the time of ascertainment/recruitment. Self-reported IM history and immune response genotypes were provided by the InterLymph Data Coordinating Center at Mayo Clinic. Odds ratios (OR) were estimated using multivariate logistic regression, and interactions were estimated using the empirical Bayes method. P_ACT was used to account for multiple comparisons.

Results: There was evidence of an interaction effect between IM history and two variants on T-cell lymphoma (TCL) risk: rs1143627 in interleukin-1B (IL1B) (p_interaction = 0.04, OR_interaction = 0.09, 95% confidence interval [CI] 0.01, 0.87) and rs1800797 in interleukin-6 (IL6) (p_interaction = 0.03, OR_interaction = 0.08, 95% CI 0.01, 0.80). Neither interaction effect withstood adjustment for multiple comparisons. There were no statistically significant interactions between immune response genotypes and IM on other NHL subtypes.

Conclusions: Genetic risk variants in IL1B and IL6 may affect the association between IM and TCL, possibly by influencing T-cell activation, growth, and differentiation in the presence of IM, thereby decreasing risk of immune cell proliferation.

Keywords: Gene–environment interaction; Infectious mononucleosis; Interleukin-1beta (IL1B); Interleukin-6 (IL6); Non-Hodgkin lymphoma; T-cell lymphoma.

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Bayes Theorem
Case-Control Studies
Female
Genotype
Humans
Infectious Mononucleosis / genetics*
Infectious Mononucleosis / immunology
Lymphoma, Non-Hodgkin / genetics*
Male
Middle Aged
Risk Factors
Self Report
Young Adult

Abstract

MeSH terms

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