Genetic Susceptibility to Hodgkin Lymphoma.

A case-control study of young adult Hodgkin lymphoma (diagnosed before age 50) in twins was conducted to determine if cases and their unaffected identical twins demonstrated dominance of Th1, Th2 or regulatory cytokines compared to unrelated controls. We collected blood specimens from sets of young adult Hodgkin lymphoma cases (n=60), their unaffected identical twins (n=60) and unrelated controls (n=60) and measured IL-6, IL-8, IL-10, and IL-12 levels in PHA-stimulated PBMC supernatant by ELISA. IL-6, IL-10 and IL-12 promoter polymorphisms were determined using PCR and either Taqman or Pyrosequencing. Mean levels of cytokines were compared using an analysis of covariance and genotypes were compared using multivariate logistic regression (SAS). Both cases and their unaffected twins had higher levels of IL-8, but lower levels of IL-12, compared to controls. Unaffected twins of cases had IL-6 levels that were 86% higher than those of controls (p=0.02), however cases’ levels were lower than controls (altered by treatment). Cases and their twins were three times more likely to have an IL-6 genotype associated with higher levels and 2.6 times more likely to have an IL-12 genotype associated with lower levels, compared to controls (Table 2). There were no significant differences in IL-10 levels or genotypes between cases and controls. A genetically determined skewing toward increased inflammatory cytokines (IL-6 and IL-8) and decreased Th1 cytokines (IL-12) is associated with increased susceptibility to young adult Hodgkin lymphoma.

Table 1. Mean and % Difference in Cytokine Levels in Hodgkin Lymphoma Cases, their Unaffected Identical Twins, and Controls

Table 2. Cytokine Genotype and Risk of Young Adult Hodgkin Lymphoma in Cases v. Controls