Thursday, 17 March 2016

ResearchSpeak: Hodgkin's lymphoma and MS share genetics

Did you know that Hodgkin's lymphoma and MS run in the same families? #ResearchSpeak #MSBlog #MSResearch

"The following genomic study suggests that there is an overlap between Hodgkin's lymphoma (HL) and MS, at least in terms of genetic susceptibility. This is interesting as these diseases share some epidemiological features, (1) they are strongly associated with EBV, (2) cluster in the same families, (3 ) occur in the same age group and (4) are linked to latitude and hence ultraviolet light or low vD levels. What the study shows is that the genetic susceptibility overlap is mainly in the HLA region. More interesting is that genetic susceptibility to developing HL is closer to other autoimmune diseases rather than to solid cancers. Could this mean that HL is an infectious disease? This is highly likely as a significant proportion of HL is due to EBV. How do I interpret these findings? I am not sure, but it may point to complex biology and suggests that people who are susceptible to developing MS or HL have problems dealing with EBV and as a result a proportion of them go onto to develop overt disease. The million dollar question is that if we can vaccinate these people with an appropriate EBV vaccine prior to them getting EBV would we prevent them developing MS and/or HL? May be we can answer this question in our lifetime."

"If we ever work out how EBV causes MS we may find clues to how it causes HL and vice versa."


Khankhanian et al. Meta-analysis of genome-wide association studies reveals genetic overlap between Hodgkin lymphoma and multiple sclerosis. Int J Epidemiol. 2016 Mar 12. pii: dyv364.

BACKGROUND: Based on epidemiological commonalities, multiple sclerosis (MS) and Hodgkin lymphoma (HL), two clinically distinct conditions, have long been suspected to be aetiologically related. MS and HL occur in roughly the same age groups, both are associated with Epstein-Barr virus infection and ultraviolet (UV) light exposure, and they cluster mutually in families (though not in individuals). We speculated if in addition to sharing environmental risk factors, MS and HL were also genetically related. Using data from genome-wide association studies (GWAS) of 1816 HL patients, 9772 MS patients and 25 255 controls, we therefore investigated the genetic overlap between the two diseases.

METHODS: From among a common denominator of 404 K single nucleotide polymorphisms (SNPs) studied, we identified SNPs and human leukocyte antigen (HLA) alleles independently associated with both diseases. Next, we assessed the cumulative genome-wide effect of MS-associated SNPs on HL and of HL-associated SNPs on MS. To provide an interpretational frame of reference, we used data from published GWAS to create a genetic network of diseases within which we analysed proximity of HL and MS to autoimmune diseases and haematological and non-haematological malignancies.

RESULTS: SNP analyses revealed genome-wide overlap between HL and MS, most prominently in the HLA region. Polygenic HL risk scores explained 4.44% of HL risk (Nagelkerke R2), but also 2.36% of MS risk. Conversely, polygenic MS risk scores explained 8.08% of MS risk and 1.94% of HL risk. In the genetic disease network, HL was closer to autoimmune diseases than to solid cancers.

CONCLUSIONS: HL displays considerable genetic overlap with MS and other autoimmune diseases.

14 comments:

  1. My father had Hodgkin's disease the year I was diagnosed. I didn't live with him so if it's environmental it must be something in London.

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  2. Prof G, what do you make the disability welfare cuts? Is it getting harder to have MS in modern Britain?

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    1. Re: "Disability cuts."

      Yes, it is harder to have MS in Britain, but not as hard as it is to have MS in Greece or Syria. The grass is always greener on the other side. The current government clearly wants to reduce the size of the state, which means the third sector (charities, family, etc.) will need to step in. In countries that aren't socialist, i.e. where you can't rely on the state, families and friends do the heavy lifting. That is what is going to have to happen.

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    2. Welfare benefits used to be given to people to help them lead as normal life as possible. What was supposed to happen was the extra money would help towards transport and domestic chores that enabled them to work and pay taxes. Without the help disabled people that could work in an office job won't be able to afford transport costs etc, therefore unable to contribute to the economy. The government has changed the reason for paying the benefit. What most of the public don't realise is that tomorrow they could become disabled with a stroke and after paying taxes all their life, they join the rest of us that paid our fair share and become a drain on society. It's a shame the chancellor thinks it's more important to reduce capital gains tax for rich people.

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    3. Prof G, that is a scary premonition. Life will indeed become insufferable for those with chronic health conditions. We're aging too, which means more social uncertainty.

      We as a society should be very afraid. I can't believe the British passivity to this matter.

      Where the heck its Dr Dre?

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    4. Sounds like there's going to be a U-turn on this as a number of Tory backbenchers are minded to rebel and only a small number would be needed to overturn the slim Tory majority.

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    5. Do you really think Tory MPs will vote against the cuts and put their career ambitions on the line?

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  3. Prof. G when I read about a possible connection between Lymphomas, EBV and MS, I found quite intriguing, as I remembered having met some people with MS who have had cancer and the most common form of cancer among them was precisely the Lymphomas...
    Maybe talking to Oncologists area can give further direction to some unanswered questions about the connection MS/EBV ...

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  4. Is the EBV vaccine being developped or what is the current stage of research?

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  5. "What causes Hodgkin lymphoma? (source NHS Choices)
    The exact cause of Hodgkin lymphoma is unknown. However, your risk of developing the condition is increased if:
    you have a medical condition that weakens your immune system
    you take immunosuppressant medication
    you've previously been exposed to a common virus called the Epstein-Barr virus – which causes glandular fever"

    The question that comes to mind: Considering the Hodgkin overlap with MS, what is the co-morbidity rate of MSers treated with an immunosuppressant?

    Tony Fonda

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  6. "...if we can vaccinate these people with an appropriate EBV vaccine prior to them getting EBV would we prevent them developing MS... "

    I find it difficult to imagine how this can be tested:
    - Let's say that an anti-EBV vaccine with 100% efficacy is developed. You should vaccinate hundreds of thousands of people and not one of them should exhibit MS, in order to prove that EBV causes MS. Not on this world.
    - In the more plausible scenario of an anti-EBV vaccine that offers < 100% protection, you should run a placebo controlled trial, right? So, you should form two large groups of uninfected people, without MS, that should have equal probability to include every possible number of future MS patients (!), and then administer the vaccine to one of these groups and placebo to the other. Now, let's say that X% of the vaccine group and Y% of the placebo group develop MS, and X<Y. How can you prove that someone would be MS free thanks to the vaccination and not because he simply wouldn't get MS in any way?

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  7. Do you have any hypotheses as to how EBV might trigger HL? How about MS?

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    1. EBV is a known carcinogen, it is the known cause of Burkitt's lymphoma. It is a herpes virus like HPV which also causes cancer. HL lumps contain very few actual cancer cells but these disrupt the immune system locally so they are surrounded by many other immune cells. The cancer cells know as Reed–Sternberg cells were originally b cells. B cells are infected by Epstein Barr causing them to become immortal, increasing the risk of cancer developing. The exact mechanism to get between a b cell and a Reed–Sternberg cell is not known. HL can cause long range immune effects well away from the actual lymphoma including persistent fatigue and whole body itching. The sub type of HL where EBV is most strongly implicated is 'mixed cellularity'. It would have been interesting to see a break down by sub type.

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  8. I had hodgkins lymphoma in 1990 and just been diagnosed with MS ! Have had a developing foot drop over the last few years but was told in 2011 after MRI that I had radiation myelopathy as a result of the radiation treatment that I had in 1990. Now been told it is not that but MS instead.
    Never had glandular fever though !

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