HEREDITARY LYMPHOMA

Hereditary Lymphoma Risk — familial clustering is well-documented across Hodgkin and non-Hodgkin lymphoma, with HLA genotype, immune regulatory genes, and inherited immunodeficiency syndromes contributing to genetic susceptibility.

Whole genome sequencing evaluates HLA haplotypes, immune regulatory variants, primary immunodeficiency genes, and lymphoma susceptibility loci — providing comprehensive genetic risk assessment for lymphoma predisposition.

HLA
ATM
SH2D1A
FAS
WAS

About this condition

Lymphoma — Hereditary Risk

Lymphoma shows significant familial clustering. First-degree relatives of Hodgkin lymphoma patients have approximately 3-9x increased risk. Non-Hodgkin lymphoma (NHL) shows 2-3x familial risk. HLA class I and II variants are the strongest common genetic determinants — HLA-A*01, HLA-DPB1*03:01 affect Hodgkin lymphoma risk, while HLA-B*08 and various HLA class II alleles influence NHL susceptibility.

Primary immunodeficiency disorders substantially increase lymphoma risk: ataxia-telangiectasia (ATM — 100x lymphoma risk), Wiskott-Aldrich syndrome (WAS), common variable immunodeficiency (TNFRSF13B/TACI), X-linked lymphoproliferative syndrome (SH2D1A/SAP), and autoimmune lymphoproliferative syndrome (ALPS — FAS, FASLG, CASP10). These monogenic conditions predispose to lymphoma through impaired immune surveillance.

Emerging GWAS loci for lymphoma susceptibility include variants affecting B-cell biology (MTHFR, LPP, PVT1), apoptosis pathways (BCL2, CASP8), and immune regulation (CTLA4, TNF). Polygenic risk scores combining these variants with HLA genotype can identify individuals at significantly elevated lymphoma risk.

Ataxia-telangiectasia (ATM) carriers have ~100x increased lymphoma risk. Any child with recurrent infections, ataxia, and telangiectasias should have ATM testing urgently — lymphoma surveillance is critical.

Gene locus: HLA region (6p21.3), ATM (11q22.3), SH2D1A (Xq25), FAS (10q23.31), WAS (Xp11.23)

Lymphoma genetics spans HLA typing, primary immunodeficiency genes, and GWAS susceptibility loci. WGS captures all three dimensions in a single comprehensive test.

Primary immunodeficiency genes confer extreme lymphoma risk — identification enables surveillance and prevention

ATM (ataxia-telangiectasia), SH2D1A (XLP), and FAS (ALPS) carriers have dramatically elevated lymphoma risk. Identification through WGS triggers appropriate lymphoma surveillance, avoidance of radiation (ATM), and management of the underlying immunodeficiency.

HLA genotype is the strongest common genetic determinant of lymphoma risk — WGS provides complete HLA typing

HLA haplotypes influence both Hodgkin and non-Hodgkin lymphoma susceptibility through effects on immune surveillance and antigen presentation. Complete HLA typing through WGS provides the most informative common genetic lymphoma risk assessment.

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