Does having autoimmune disorder (atopic disease in my mind, but also otherwise) lead to an increased risk of immune cell cancer?

Submitted by MoBuckeye t3_10wp4sh in askscience

So I have an MD and I tried to figure this out to no avail. My 18 yo at the time sister battled with Hodgkins lymohoma while I was in med school. Her only history was eczema, asthma, seasonal allergies (atopic disease). I was wondering, does high turnover of cells due to increased immune response and cell death/rebirth increase risk of immune cell mutation leading to lymphoma? Is there a link between the two?? I feel like this is the beginning of a retrospective research study...

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oviforconnsmythe t1_j7onh5c wrote

In theory, yes increased turnover/expansion of immune cells in inflammatory contexts can lead to increased frequency of oncogenic mutations that turn into hematological cancers. Each round of cell division has the possibility to introduce oncogenic mutations (mutations in genes that transform a normal cell into a cancerous one) as a result of DNA replication errors. But there are also many mechanisms to correct such errors or kill off cells with oncogenic mutations. So the chance of cancers arising solely from this mechanism are low and there are a number of other factors that play more substantial roles in cancer formation.

The conditions you listed are associated with chronic inflammation. Chronic inflammation has been widely established as a risk factor for many different cancers. While increased cell turnover (e.g. immune cells in inflammatory settings) can potentially enhance the risk of oncogenic mutations, the inflammatory microenvironment (i.e. both cellular composition and factors secreted by theses cells in inflamed tissue) itself is likely a much more substantial driver of cancer formation. For example, remodeling of the extracellular matrix (ie the scaffold that forms tissue structure) is an important feature of inflammation but is also critical for metastasis and/or formation of blood vessels (angiogenesis) that could feed a growing tumor. Immune cells in inflamed tissue can secrete MMPs (which break down and remodel the extracellular matrix) and angiogenic factors. While the immune system/inflammation is essential to kill cancerous cells in tumors, some subsets of immune cells present in the tumor microenvironment (TME) secrete factors that suppress the anti-cancer immune response. Chronic inflammation can enhance or induce these suppressor subsets. Here's a nice review on the mechanisms by which inflammation drives cancer formation.

For your question specifically, there is a JAMA paper that reports an association between atopic eczema and lymphoma risk. It's not a particularly strong association, but they did find that the lymphoma risk correlates with eczema severity. Given that the potency of the inflammatory response determines severity, this is in line with what I mentioned above. In theory, controlling inflammation (which is the principle behind most eczema therapies) should reduce the cancer risk. But broad immune suppression increases the risk of infection. Infection with Epstein-Barr Virus (EBV-one of the causative agents of mononucleosis) is a well-recognized risk factor of development of both Hodgkin's and Non-Hodgkin's lymphoma. EBV infects lymphocytes and encodes proteins that contribute to cancer cell transformation and augment the TME to make it more suppressive. Other viruses have also been associated with this before. EBV driven lymphomas are a potential complication in transplant patients (which receive potent immunosuppressant drugs to increase transplant success).

So overall, yes chronic inflammatory diseases like eczema or asthma can potentially promote cancer but not (solely) through the mechanism you describe. I hope I've been able to help your prospective study (which I think you should definitely write, its a really neat hypothesis)!

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lobster_johnson t1_j7qyau4 wrote

Some autoimmune disorders like rheumatoid arthritis and psoriasis are indeed associated with an increased risk of cancer. The link between psoriasis and cancer was considered relatively recently.

A Danish systemic review, Prevalence, Incidence, and Risk of Cancer in Patients With Psoriasis and Psoriatic Arthritis: A Systematic Review and Meta-analysis (Vaengebjerg et al) made these observations about psoriasis:

> From a total of 112 studies included in the analysis, overall cancer prevalence among persons with psoriasis was 4.78% (95% CI, 4.02%-5.59%). When keratinocyte cancer was excluded from the analysis, the prevalence of overall cancer decreased to 4.06% (95% CI, 3.31%-4.87%). > > From the 14 studies that reported risk estimates in the context of overall cancer or included a reference group, the risk ratio for cancer development in those with psoriasis was 1.21 (95% CI, 1.11-1.33), but decreased to 1.14 (95% CI, 1.04-1.25) when keratinocyte cancer was excluded.

Here is an article summarizing the findings. Lymphomas and skin cancers are among the top cancers seen in among psoriasis patients.

A challenge with these studies is that they often look at people with severe manifestations of the disease, or that are being treated with immunosuppressive drugs such as biologics. The above study tries to account for the latter, but not (if I remember correctly) the former. While I don't have a citation in front of me, the association is mostly with severe psoriasis, not mild psoriasis.

Rheumatoid arthritis is another autoimmune disease tied to cancer. RA patients have double the risk of developing [lymphomas] https://www.arthritis.org/health-wellness/about-arthritis/related-conditions/other-diseases/arthritis-and-cancer-risk in particular.

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Aardbeienshake t1_j7r3vud wrote

Replying to oviforconnsmythe (#1,751,836)

Thanks for this thorough explanation. I had EBV and resulting mono when I was a teen, and had non-hodgkin lymphoma in my twenties. I knew back then that my mono (which was atypically severe) was a contributor, but did not know why. Interesting read!

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sciguy52 t1_j7s5i0o wrote

Replying to [deleted] (#1,757,009)

Not more than anyone else for the most part. 80% of the adult population has the EBV virus inside them whether they know it (by having had mono) or not (young people can be asymptomatic. EBV related cancers are more typical for people with immune suppression of some sort like drugs associated with an organ transplant, AIDS, or drugs used to treat autoimmune disease. That is when you see a higher incidence of these EBV associated cancers.

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imhereforthefood2718 t1_j7t0uds wrote

I intend to come back to this since this isn't nearly as thorough of answer as I'd like it to be.

Regardless, at least in my didatics, we were taught that there is a higher incidence of hematological malignancies, such as AML and CML, in those with autoimmune diseases due to the mechanism you described.

I can't remember the specific paper at the moment, but here are a few others: https://pubmed.ncbi.nlm.nih.gov/31181268/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366644/

There's at least enough correlative evidence that this association has permeated into step and board exams.

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