Genetic Study of Families With High Frequency of Hodgkin Lymphoma

Study Overview
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Brief Summary
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Hodgkin lymphoma (HL) is a relatively rare disorder with known familiar aggregation (i.e. HL in more than one child, or parent and child). Because affected individuals in familial HL are genetically related, the existence of such families has long been considered as evidence in support of a genetic basis of HL susceptibility. However, it is largely unknown which genetic variations are responsible for recurring HL in families. Because the effects of genetic variants are likely to be strong in familial HL, identification of such variations will potentially reveal biological pathways critical to the pathogenesis of HL. PRIMARY OBJECTIVE: To perform genome-wide sequencing of families with recurring Hodgkin lymphoma cases (affected as well as non-affected family members) to identify potential disease-causing germline genetic variations. SECONDARY OBJECTIVE: To describe demographic and clinical features of the affected families.

Detailed Description
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This study entails a clinical interview and submission of a peripheral blood or saliva sample for non-tumor DNA. Participants diagnosed with HL at outside institutions will be requested to sign a release form to allow the outside institution to send their pathology report confirming their HL diagnosis. If available, previously banked tumor tissue samples will be utilized to assess genetic alterations related to HL. Detailed history will be obtained (e.g., demographics, environmental exposures, cancer risk factors, and family pedigree) to facilitate the analysis of phenotype-genotype correlations, taking into account potential confounding factors. Investigators will examine the germline and possibly the tumor DNA of each individual participant and use the data from all participants to determine if a gene change is related to HL.

Official Title
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Genetic Study of Families With High Frequency of Hodgkin Lymphoma

Conditions
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Hodgkin Lymphoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with HL diagnosed ≤ 21 years of age with a first-degree relative also diagnosed with HL. Family members of the patient, either affected or unaffected by a malignancy who agree to participate in the study. Research participant or legal guardian, as appropriate, must provide informed consent for this protocol. Exclusion Criteria: Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with Hodgkin Lymphoma<br>Those with a confirmed diagnosis of Hodgkin Lymphoma (HL) and family members who consent and enroll in this study. | |
| Family Members without Hodgkin Lymphoma<br>Those unaffected by HL will serve as a control group to compare with those with HL. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Germline genetic variations | Whole exome sequencing of affected and unaffected individuals in these families will be performed. Genetic variants potentially related to HL will be identified on the basis of its co-segregation with HL disease status (e.g., unique variants in individuals affected by HL would be considered as risk variants). Family members without HL (regardless of any other history of malignancy) will be considered as control and be compared against members with HL. | Once, within 1 month of enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genetic studies, Pediatric