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Int J Cancer. 2015 Nov 1;137(9):2163-74. doi: 10.1002/ijc.29589. Epub 2015 May 19.

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

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Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN.
University of Minnesota Masonic Cancer Center, Minneapolis, MN.
Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM.
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.
Division of Pediatric Hematology and Oncology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN.
Cancer Prevention Institute of California, Fremont, CA.
Department of Health Research and Policy (Epidemiology), Stanford University, Stanford, CA.
Registre Des Hémopathies Malignes De La Gironde, Institut Bergonié, Bordeaux, France.
Centre INSERM U897, CIC 1401, Centre D'investigation Clinique, Bordeaux, France.
Division of Epidemiology, Biostatistics, and Preventive Medicine, Department of Internal Medicine, University of New Mexico, Albuquerque, NM.


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.


Hodgkin lymphoma; children; family cancer history; genetic predisposition

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