A cancer of the cells that make antibodies, often found by accident on a blood test, and among the common cancers one of the most strongly familial. The genes that come out of the scans are immunity genes, which is the answer the biology would predict.
What this condition connects to
Prevalence
A meta-analysis of six genome-wide association studies, imputed against a merged 1000 Genomes and UK10K reference panel and totalling 6,200 cases and 17,598 controls after replication, identified nine new risk loci and implicated dysregulation of immunity genes (Law et al., Nature Communications 2017, PMID 28165464).
Inheritance
Common variants, each shifting an already small baseline risk slightly, on a cancer with an unusually strong familial component for a common one. Distinct from the changes that guide treatment, which are acquired by the tumour cells rather than inherited.
Chronic lymphocytic leukaemia is a cancer of B lymphocytes — the white cells that make antibodies. It is the commonest leukaemia in adults in Western countries, it usually appears later in life, and it is frequently discovered by accident when someone has a blood test for something else and the lymphocyte count is high.
Many people with it need no treatment for years, and some never do. That matters for how this page should be read.
Unusually familial, for a common cancer
Most common cancers have a modest inherited component. This one has more, which is part of why it has been studied genetically as hard as it has, and why a fair share of the risk has been located.
A 2017 meta-analysis combined six genome-wide association studies, imputed against a merged reference panel, and totalled 6,200 cases and 17,598 controls after replication. It identified nine new risk loci.
And the genes are immunity genes
The paper's own title says what came out: dysregulation of immunity genes. For a cancer of the antibody-producing cells, that is the answer the biology predicts, and getting the predicted answer from an unbiased genome-wide scan is a real result rather than a boring one.
Among the genes this site holds under this trait:
IRF4 — a transcription factor that directs B cells through their final differentiation into antibody-secreting cells. It is one of the strongest and earliest-found signals for this disease.
LEF1 — part of the Wnt signalling pathway and used in the laboratory as a marker for these cells.
SP110 — a nuclear body protein involved in immune response.
POT1 — a different kind of clue: it protects the ends of chromosomes. Telomere biology turns up repeatedly in cancer genetics and is not an immunity story at all.
Clinical detail
How to read this page if you have had a blood test. A raised lymphocyte count is common and usually not cancer. Chronic lymphocytic leukaemia is diagnosed by flow cytometry on a blood sample, not by a count and not by a genotype, and where it is found many people are monitored rather than treated — sometimes for many years. Nothing here changes what a blood result means, and the variants on this page shift a small baseline risk by small amounts.
What inherited risk means for a cancer like this
Nine loci from a large study sounds like a lot until you compare it with the risk the loci account for. Each shifts the odds slightly. Between a person carrying more of the risk-associated forms and a person carrying fewer, the difference is a change in an already low probability, spread across a lifetime, and it does not become a reason to test or to screen.
Where inherited risk does become clinically relevant is a family with several affected close relatives, which is a conversation with a haematologist and not a page.
What this page cannot do
It cannot detect leukaemia. That is a blood test and flow cytometry.
It cannot tell you your risk. The loci here move an already small baseline slightly and are not used in any clinical risk model.
It says nothing about treatment. The genetics that guides treatment in this disease is different genetics entirely — changes acquired by the tumour cells themselves, such as TP53 disruption and the mutation status of the immunoglobulin genes. Those are tested in the cancer, not inherited, and a common-variant catalogue does not carry them.
Related variants MyGeneLog checks for
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Chronic Lymphocytic Leukaemia comes down to these specific, well-studied positions — not a diagnosis. 26 positions are linked to this page; the ones this page's own text discusses are shown first.
Nature communications · 2017 · PMID 28165464 · open access
Frequently asked questions
My lymphocyte count was high. Does that mean leukaemia?
Usually not. A raised lymphocyte count is common and has many causes, most of them infections. Chronic lymphocytic leukaemia is diagnosed by flow cytometry on a blood sample rather than by a count, and where it is found many people are monitored rather than treated, sometimes for years.
Can a DNA test tell me if I will get this?
No. The variants here shift an already small baseline risk by small amounts, and none of them is used in any clinical risk model. There is no screening programme for this disease and no genotype that would justify one.
Why are the genes all immune genes?
Because the disease is a cancer of B lymphocytes, the cells that make antibodies. A genome-wide scan makes no assumption about which genes it will find, and it found immunity genes — IRF4 and LEF1 among them. Getting the answer the biology predicts from a method that could not have been steered towards it is a real result.
Does this page say anything about treatment?
No, and the distinction matters. Treatment in this disease is guided by changes the tumour cells acquire — TP53 disruption and immunoglobulin gene mutation status — which are tested in the cancer itself. Those are not inherited and a common-variant catalogue does not carry them.
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