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

Amy M. Linabery, Erik B. Erhardt, Michaela R. Richardson, Richard F. Ambinder, Debra L. Friedman, Sally L. Glaser, Alain Monnereau, Logan G. Spector, Julie A. Ross, Seymour Grufferman

Research output: Contribution to journalReview article

Abstract

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.
Original languageEnglish (US)
Pages (from-to)2163-2174
Number of pages11
JournalInternational Journal of Cancer
Volume137
Issue number9
StatePublished - 2015

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Hodgkin Disease
Confidence Intervals
Pediatrics
Human Herpesvirus 4
Neoplasms
Genetic Predisposition to Disease
Environmental Exposure
Pedigree
Cluster Analysis
Parents
Logistic Models
Odds Ratio
Observation
RNA
Interviews

Keywords

  • children
  • family cancer history
  • genetic predisposition
  • Hodgkin lymphoma

Cite this

Linabery, A. M., Erhardt, E. B., Richardson, M. R., Ambinder, R. F., Friedman, D. L., Glaser, S. L., ... Grufferman, S. (2015). Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children's Oncology Group study. International Journal of Cancer, 137(9), 2163-2174.

Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children's Oncology Group study. / Linabery, Amy M.; Erhardt, Erik B.; Richardson, Michaela R.; Ambinder, Richard F.; Friedman, Debra L.; Glaser, Sally L.; Monnereau, Alain; Spector, Logan G.; Ross, Julie A.; Grufferman, Seymour.

In: International Journal of Cancer, Vol. 137, No. 9, 2015, p. 2163-2174.

Research output: Contribution to journalReview article

Linabery, AM, Erhardt, EB, Richardson, MR, Ambinder, RF, Friedman, DL, Glaser, SL, Monnereau, A, Spector, LG, Ross, JA & Grufferman, S 2015, 'Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children's Oncology Group study', International Journal of Cancer, vol. 137, no. 9, pp. 2163-2174.
Linabery, Amy M. ; Erhardt, Erik B. ; Richardson, Michaela R. ; Ambinder, Richard F. ; Friedman, Debra L. ; Glaser, Sally L. ; Monnereau, Alain ; Spector, Logan G. ; Ross, Julie A. ; Grufferman, Seymour. / Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children's Oncology Group study. In: International Journal of Cancer. 2015 ; Vol. 137, No. 9. pp. 2163-2174.
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title = "Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children's Oncology Group study",
abstract = "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.",
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T1 - Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children's Oncology Group study

AU - Linabery, Amy M.

AU - Erhardt, Erik B.

AU - Richardson, Michaela R.

AU - Ambinder, Richard F.

AU - Friedman, Debra L.

AU - Glaser, Sally L.

AU - Monnereau, Alain

AU - Spector, Logan G.

AU - Ross, Julie A.

AU - Grufferman, Seymour

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - children

KW - family cancer history

KW - genetic predisposition

KW - Hodgkin lymphoma

M3 - Review article

VL - 137

SP - 2163

EP - 2174

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 9

ER -