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

Background: We explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case-control analysis. Methods: 7926 NHL patients and 10 018 controls from 12 studies were included. Self-reported IM history and genotypes were provided by the InterLymph Data Coordinating Center at Mayo Clinic. Odds ratios (OR) were estimated using multivariate logistic and linear regression, and interactions with the empirical Bayes method. Bonferroni corrections and pACT were 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 (pinteraction= 0.02, ORinteraction = 0.09, 95% confidence interval [CI] = 0.01, 0.87) and rs1800797 in interleukin-6 (pinteraction = 0.02, ORinteraction=0.08, 95% CI = 0.01, 0.80). Neither interaction effect withstood adjustment for multiple comparisons. Among controls, increasing socioeconomic status (OR = 1.69, 95% CI = 1.48, 1.93) and female sex (OR = 1.53, 95% CI = 1.26, 1.87) were positively associated with IM. Large sibship size (3+) was inversely associated with IM among controls born before 1960 (OR<1960 = 0.40, 95% CI = 0.24, 0.67), but not after. Conclusions: Genetic risk variants in IL1B and IL6 may affect the association between IM and TCL. Risk factors for IM are consistent with lower Epstein-Barr virus exposure in early life; the association with female sex is unexplained. Keywords: Infectious mononucleosis, non-Hodgkin lymphoma, T-cell lymphoma, genotype, interleukin 1B, interleukin 6, siblings, family size, socioeconomic status Key Messages • A suggestion that genetic variation in interleukin-1B (IL1B) and interleukin-6 (IL6) may attenuate the association between infectious mononucleosis and T-cell lymphoma requires confirmation with larger numbers. • Increasing socioeconomic status and female sex are independently associated with self-reported infectious mononucleosis. • The number of siblings is inversely associated with self-reported infectious mononucleosis among those born before 1960 but not those born after.