Abstract 2631

Background:

Epstein-Barr Virus (EBV) is a risk factor for some types of Hodgkin lymphoma (HL). Host response to the virus may play a role in pathogenesis and is in part determined by genetic factors. Therefore, using only traditional unrelated controls may not be appropriate.

Methods:

We compared EBV DNA copy number in peripheral blood mononuclear cells (PBMCs) collected from 63 young adult HL patients in remission and their unaffected co-twins, and 43 spouse controls. Viral load was measured with TaqMan quantitative PCR assays, tested in triplicate and reported as viral copies per million cells. Samples positive in all 3 replicates were classified as positive, and those positive in 1–2 samples were classified as qualitative positive (QP). EBV copy number was log-transformed for some analyses. A binomial proportion test was used to compare EBV copy number in cases and their unaffected co-twins (n=50 like-sex pairs). Conditional (case vs. unaffected co-twin) and unconditional logistic regression (case and unaffected co-twin vs. spouse controls) were used to estimate the effect of EBV copy number on risk as a categorical (positive, QP, or negative) or continuous variable (SAS 9.1). Unconditional logistic regression analyses were adjusted for sex and age.

Results:

26% of case, 18% of unaffected co-twins and 9% of spouse controls had positive EBV copy number measurements. Like-sex young adult HL cases had higher EBV copy numbers compared to their unaffected co-twins (P = 0.04). When EBV copy number was considered as a categorical variable, both cases and monozygotic unaffected co-twins were more likely to be positive compared to controls (cases v. controls: Odds Ratio [OR] = 3.2, 95% confidence intervals [CI] = 0.9, 11.1; unaffected co-twins v. controls: OR= 3.6, 95% CI= 0.9, 14.6). However, there was little difference between dizygotic unaffected co-twins and controls (OR= 0.7, 95% CI = 0.5, 5.5).

Conclusions:

That young adult HL cases had higher EBV DNA copies than their unaffected co-twins implies that an acquired pre-disease factor or disease affect altered the host response to EBV. However, that both cases and unaffected co-twins had higher EBV DNA copies compared to controls suggests that there is also a heritable component to the host response to EBV.

HL cases > co-twins (acquired or disease effect)

HL cases and co-twins > controls (heritable effect)

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Disclosures:

No relevant conflicts of interest to declare.

Topics:
herpesvirus 4, human, hodgkin's disease, twins, young adult, copy number polymorphism, dna, disease remission, genetic aspects, polymerase chain reaction, viral load result

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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