Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children's Oncology Group study

Family history of lymphoid neoplasm (LN) is a strong and consistently observed Hodgkin lymphoma (HL) risk factor, although it has been only marginally examined in pediatric/adolescent patients. Here, healthy control children identified by random digit dialing were matched on sex, race/ethnicity and age to HL cases diagnosed at 0-14 years at Children's Oncology Group institutions in 1989-2003. Detailed histories were captured by structured telephone interviews with parents of 517 cases and 783 controls. Epstein-Barr virus (EBV) RNA detection was performed for 355 available case tumors. Two analytic strategies were applied to estimate associations between family cancer history and pediatric/adolescent HL. In a standard case-control approach, multivariate conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs). In a reconstructed cohort approach, each relative was included as a separate observation, and multivariate proportional hazards regression was used to produce hazard ratios (HRs) and 95% CIs. Using the latter, pediatric/adolescent HL was associated with a positive family history (HR=1.20, 95% CI: 1.06-1.36), particularly early-onset cancers (HR=1.30, 95% CI: 1.06-1.59) and those in the paternal lineage (HR=1.38, 95% CI: 1.16-1.65), with a suggested association for LN in first-degree relatives (HR=3.61, 95% CI: 0.87-15.01). There were no discernable patterns for EBV+ versus EBV- HL. The clustering of LN within pedigrees may signal shared genetic susceptibility or common environmental exposures. Heritable genetic risk variants have only recently begun to be discovered, however. These results are consistent with other studies and provide a compelling rationale for family-based studies to garner information about genetic susceptibility to HL. What's new? Children and adolescents with Hodgkin lymphoma (HL) often have a family history of lymphoid neoplasm (LN), but the role of familial cancer history in pediatric/adolescent HL is not well defined. Here, HL in children and adolescents was found to be associated with an increased number of cancers in first- and second-degree relatives. Associations were most notable for early-onset cancers, cancers in the paternal lineage and LN in first-degree relatives. Tumor Epstein-Barr virus status had no bearing on the associations. The results suggest that children and adolescents with familial clustering of LNs share genetic and environmental risk factors with relatives.