The most common and clinically aggressive lymphoma subtype, whose inherited risk loci point at immune recognition pathways — including two independent signals at the same 8q24.21 region as the MYC oncogene, famous for a completely different, acquired role in this disease.
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive, though often curable with modern chemoimmunotherapy. This page holds 4 inherited (germline) variants from one large study.
A 2014 study combined three new genome-wide association studies with a previous scan — 3,857 cases and 7,666 controls in total — then further genotyped nine promising signals in another 1,359 cases and 4,557 controls. Five independent SNPs across four loci reached genome-wide significance. The strongest, rs116446171 at 6p25.3 in EXOC2, had by far the smallest p-value of the study. rs79480871, near NCOA1, was a second independent signal.
The study's remaining two loci, rs13255292 and rs4733601, are both independent signals at 8q24.21 — a region the paper itself attributes to PVT1, though this site's own catalogue lists the immediately adjacent gene MYC for the same two variants; both genes sit at this locus and both are commonly cited for GWAS hits here. Worth being precise about what this actually is: MYC is one of the most consequential genes in DLBCL biology through acquired chromosomal rearrangements — a MYC rearrangement, especially alongside one in BCL2 or BCL6 ("double-hit" lymphoma), marks a more aggressive, harder-to-treat form of the disease. These two inherited common variants sit near the same gene region but are a completely different kind of change — weak, population-level, present from birth — not evidence of, or a substitute for, the acquired rearrangement testing that actually matters clinically.
The study's own stated conclusion is that these loci, taken together, point toward pathways of immune recognition and immune function in how DLBCL originates — a disease of B cells, the immune system's own antibody-producing cells.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 1 more position to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Güler M et al. 2025, Blood cancer journal rs71557353 (near ZNF322) — PMID:40883272
2025-02-12 · Pfizer, official press release (ECHELON-3 trial, n=230)
FDA approves ADCETRIS combination that cuts death risk 37% in relapsed large B-cell lymphoma
Verified directly against Pfizer's own press release. On 12 Feb 2025 the FDA approved ADCETRIS (brentuximab vedotin) with lenalidomide and rituximab for relapsed/refractory large B-cell lymphoma (including DLBCL) after 2+ prior therapies, in patients not eligible for stem-cell or CAR-T therapy. In the ECHELON-3 trial (230 patients randomized), the combination reduced the risk of death by 37% versus placebo plus lenalidomide/rituximab (hazard ratio 0.63, 95% CI 0.445-0.891, p=0.0085) -- an overall-survival result, not just progression-free survival. A treatment-regimen approval, not a new genetic finding -- unrelated to the inherited variants this page describes, which are population-level susceptibility factors, not treatment-selection markers.
2026-09-18 · La Marca E, Diepstraten S, Herold M, et al. Science Advances. 2026. DOI:10.1126/sciadv.aec0722
Researchers at the Olivia Newton-John Cancer Research Institute, WEHI and Genentech built a new whole-genome CRISPR activation tool (called Partita) and used it in a mouse model of aggressive MYC-driven lymphoma. Switching on the Irx5 gene let cancer cells survive venetoclax -- a widely used blood cancer drug most established in chronic lymphocytic leukaemia (CLL), where it is a mainstay treatment -- by raising levels of a separate cell-survival protein the source reporting did not specify further. In the same mouse model, switching on any of three other genes (Runx2, Runx3, Csf1r) accelerated MYC-driven lymphoma growth. This is animal-model, drug-resistance-mechanism research rather than a human genetic-risk finding, so it is filed here as plausible context for readers of this catalogue's blood-cancer pages rather than a confirmed human variant association -- none of the four genes are yet catalogued here for a blood-cancer trait.
DLBCL is diagnosed by lymph node biopsy, and its treatment and prognosis are guided by the tumor's own acquired genetic features — chiefly MYC, BCL2 and BCL6 rearrangement status — not by the inherited variants on this page. None of the 4 germline variants here are used by any guideline to diagnose DLBCL or select treatment.
The loci described above come from a population-level genetic study comparing thousands of people with DLBCL to controls. They point at which biological systems (immune recognition, antigen presentation) shape inherited susceptibility — they do not predict whether any one person will develop the disease, and they are a different question entirely from the acquired MYC/BCL2/BCL6 rearrangement testing an oncologist actually orders on a diagnosed tumor.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Diffuse Large B Cell Lymphoma comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 4 of 5 linked studies with a resolved discovery ancestry.
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Diffuse Large B Cell Lymphoma. MyGeneLog™. https://www.mygenelog.com/conditions/diffuse-large-b-cell-lymphoma
The most common and clinically aggressive lymphoma subtype, a cancer of B cells, often curable with modern chemoimmunotherapy.
In two different ways. MYC is best known in DLBCL for acquired chromosomal rearrangements that mark more aggressive disease. Separately, this page holds two inherited common variants at the same 8q24.21 chromosomal region (near MYC and the adjacent gene PVT1) with their own, much weaker, population-level risk association -- not the same finding.
rs116446171, near EXOC2, had the smallest p-value in the largest genetic study of DLBCL to date.
No. DLBCL is diagnosed by lymph node biopsy, and treatment is guided by the tumor's own acquired genetic rearrangements. These are population-level findings from thousands of people, not a way to predict an individual case.
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