Is the parasite Toxoplasma gondii linked to brain cancer?

By Ed Yong | July 26, 2011 7:00 pm

Around a third of us are infected with a brain parasite called Toxoplasma gondii. This single-celled creature spreads to humans from cats, and has a tendency to change the behaviour of its hosts. Now, a team of scientists led by Frederic Thomas and Kevin Lafferty have found that countries where more people are infected with the parasite have higher rates of brain cancer.

This does not mean that T.gondii causes brain cancer, or even that the two are actually linked. Patricia McKinney, who studies brain cancer and was not involved in the study, says, “This is a technically sound hypothesis-generating paper and, viewed as such, is interesting. It doesn’t tell us much, other than pointing towards some further investigation.”

What is Toxoplasma gondii?

Humans can become infected with T.gondii, either through contact with soil contaminated by cat faeces, or by eating infected meat. These infections are extremely common, and up a third of the world may carry the parasite. However, rates of infection vary greatly from country to country, from just 7 percent in the UK and 11 percent in the USA, to around 67 percent in Brazil.

In the first few weeks of an infection, the parasite causes mild flu-like symptoms, if any. Afterwards, it creates cysts within the blood cells and neurons of its host, and it can persist that way for an entire lifetime without any obvious ill effects. It only causes serious problems for people with weakened immune systems, who can become seriously ill.

But T.gondii can have subtler effects on its hosts. The parasite clearly changes the behaviour of mice and rats, fatally drawing them to the scent of cats. This increases the odds that the parasite will end up in a cat, the only animal in which they can mature and reproduce. There’s some evidence that it does similar mind-bending tricks in humans. All of these associations are disputed, but previous studies have linked the parasite to: subtle personality changes; mental illnesses like schizophrenia, anxiety and bipolar disorder; a higher risk of traffic accidents; and even global differences in human culture. Now, brain cancer joins this controversial list.

What does the new study show?

Thomas and Lafferty compared national figures from 37 countries and found that brain cancers are more common in countries where T.gondii infections are more common. Brain cancer was 1.8 times more common in countries where T.gondii was most common, than in those where it was virtually absent. To take the two extremes, in South Korea, where 4 percent of people are infected, 3.4 people out of every 100,000 develop brain cancer each year. In Brazil, 67 percent of people are infected, and 5.5 out of every 100,000 develop brain cancer each year.

However, these countries also differ in other important ways. Wealthier countries have more sophisticated technology that is better able to detect brain cancer, as well as more accurate cancer registries. To account for that, Thomas and Lafferty adjusted their results for national wealth, along with latitude (T.gondii is more common in the tropics), and cell phone use (which has been spuriously linked to brain cancer). None of these adjustments changed the link between T.gondii infections and brain cancer rates.

What does this mean?

This study is an example of an “ecological study”, one of the weakest designs in the hierarchy of medical research. Looking at differences between entire countries says nothing about the risks faced by the individual people living in those countries. At best, studies like this can suggest questions that are worth addressing in the future; at worst, they are shots in the dark that neither support not disprove a hypothesis.

These particular results simply point to a correlation between T.gondii and brain cancer, and do not imply that the parasite causes the cancer. The opposite may be true – it’s not implausible that brain tumours increase the risk of T.gondii, given that such tumours can weaken the immune system, which might make parasite infections more likely. Alternatively, something else could affect the risk of both brain cancer and T.gondii infection. Once again, weakened immune systems top the list.

McKinney has some other concerns about the study. “What are the toxoplasmosis data based on?” she asks. “Are they a true reflection of prevalence or a reflection of those who have a blood test?” She also says that it “weakens any argument about cause” to look at all brain cancers together, since there are many types that are all clinically distinct and probably have different causes.

Is the link plausible?

McKinney points out that there is no explanation for how T.gondii could trigger a tumour. But the idea that a parasite could increase the risk of brain cancer is not absurd. T.gondii lives for a long time in the brain, and brain cancers take several decades to develop. T.gondii stops cells from killing themselves, and it causes a mild degree of inflammation – two of the hallmarks of cancer.

And many infections are established causes of cancer. The virus HPV causes virtually all cervical cancers along with several other types, while hepatitis B and C cause liver cancer. The bacterium Helicobacter pylori can lead to stomach cancer. Schistosoma, a group of parasitic worms, can increase the risk of bladder cancer. Some scientists have suggested that a common virus called cytomegalovirus might be linked to brain cancer, but as with T.gondii, it’s too early to say if that’s a real association or a false start.

This is not the first time that T.gondii has been linked to brain cancer, although previous studies have been small and inconsistent. An Australian team found that people with meningioma – a type of brain cancer – were twice as likely to test positive for T.gondii as people without it. However, the parasite had no bearing on the odds of glioma, another type of brain cancer. Meanwhile, American researchers found that patients with astrocytoma – the most common glioma – are more likely to have T.gondii infections.

What’s next?

Thomas and Lafferty recognise the limitations of their study. Lafferty says, “These were the best data available and we felt they were sufficient to take the first step. Working with actual brain cancer patients is an obvious next step, but it would be an expensive proposition.  It is a lot easier to justify the second, expensive step when you have some evidence for the hypothesis. We are hoping that our results motivate others in the field to do further studies.”

Brain cancer is such a rare disease that gathering enough people for a large and strong enough study is a challenge. But Lafferty thinks that there’s an easy solution at hand. “The National Cancer Institute currently has all the blood samples from brain cancer patients that one would need to do the definitive test at relatively little expense. The research hasn’t been done yet only because nobody has thought to do it.”

Even such samples might not be enough. Cancer-causing infections tend to be extremely common – take HPV and Epstein-Barr virus, for example – and they only cause diseases in a very small proportion of carriers. This means that it can be very hard to establish if an infection actually causes cancer, and we’re unlikely to get a solid coda to the the T.gondii-brain cancer story for a long while.

Update: I contacted Robert Newton, who studies infectious causes of cancer at the University of York, for a comment. He didn’t get back to me in time for publication, but I’m posting his thoughts below:

As you know, Toxoplasma gondii is a parasitic infection of cats. It can and does infect humans, but is usually most damaging in those who have underlying immunesuppression (who are not generally at increased risk of brain cancer, with the exception of lymphomas, which tend to be caused by infection with the virus EBV). It is a plausible cause of a proportion of brain cancers, since it can form cysts in the brain.

The paper by Thomas et al is very weak and, in my view, does not constitute real evidence of an association. Key issues include:

1.       There are around 120 types of brain cancer that differ with respect to their epidemiology, prognosis, clinical presentation and probably aetiology. No data on subtype were analysed

2.       Data sources – brain cancer is difficult to diagnose and data from GLOBOCAN may not be that reliable. I am unclear where the data for Toxoplasma came from although a paper is referenced

3.       Geographical correlations of this sort are notoriously difficult to interpret and no data from patients with the disease (and controls without) are presented.

This is at best, a curiosity – and I would not personally have encouraged publication of the paper

Reference: Thomas, Lafferty, Brodeur, Elguero, Gauthier-Clerc & Misse. 2011. Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common. Biology Letters http://dx.doi.org/10.1098/rsbl.2011.0588

Image from Pulmonary Pathology

Disclosure: Until recently, I worked for Cancer Research UK, looking into aspects of cancer prevention, and I still do some freelance work for them. This post is not influenced by the charity, and does not represent their views.

CATEGORIZED UNDER: Cancer, Medicine & health, Parasites

Comments (11)

  1. Nice, and very balanced story! Yes, the if correlations do have a cause it could be the other way around from what you expected. You mention: “The opposite may be true – it’s not implausible that brain tumours increase the risk of T.gondii, given that such tumours can weaken the immune system, which might make parasite infections more likely.”I think that that is not relevant in the study described, because they did not yet look at infection in cancer patient only in whole populations. Brain tumors will not explain why over 60% of the Brazilian population caries T. Gondii.

    The brain tumors might lead to a more active infection in cancer patients though, so it is something to take into account when follow-up studies are indeed planned. And it may have played a role in the Australian and American studies that you mention under “Is the link plausible?”, they really looked at infections in brain tumor patients. But that is only true if the lower immune response caused by the brain tumors not only activates an existing infection but also increases the chances to be infected in the first place.
    Since on the other hand these latter studies seem to point at certain types of brain tumors being caused by the infection, while others did not correlate, it might be relevant to check whether these types of tumors occur more in countries with high incidences of infection, like Brazil.

    Ohh and about the Daily Mail and cats ;-). Yes, the correlation could be with cats and not just with T.gondii. Cats could carry something else besides this infection that might be causative. However, I did not see a lot of cats in Brazil. But if the speculation that the behavioral changes make you be attracted to cats is true, then… having cats could be a kind of external biomarker for the infection. Like: You have cats. Checking… “Madame, your cat is at risk of being infected by you”.

  2. Simon K

    Fascinating article. I’ll be keeping an eye out for developments.

    I notice, Ed, that this is your second post in as many days relating to cancer, but it’s a topic you’ve rarely covered in the past. Is there some correlation with having left your job at Cancer Research UK?

    I wondered if you felt maybe that it’s freed you up to write more about cancer without it being seen as representing the charity’s position. Or is it that you’re more interested to look at cancer-related topics on the blog now that you’re not having to think about it all day at work? Or is it just coincidence?

  3. @Chris – Very good points.

    @Simon – A bit of everything. I’ve shied away from covering cancer-related topics on the blog before to avoid any potential conflict of interest with work. That being said, it’s rare to have two stories back-to-back, like the erionite and Toxo ones, that I felt were also suitable material for NERS. Put it this way, there haven’t been many stories that I wanted to tell on this blog but turned away because of work conflicts, at least not in epidemiology any way. There are probably a few basic biology stories that I might now start to cover.

  4. Not surprisingly, some (http://wildlifeprofessional.org/blog/?p=4139) have used this study as an opportunity to fuel the long-standing witch-hunt against feral cats.

    Setting aside the numerous shortcomings already addressed here (well done—again—Ed!), there’s something else to consider: the trends for cat ownership and incidence rate of brain cancer.

    Between 1973 and 1987, the population of pet cats in this country more than doubled from approximately 34 to 76 million. Meanwhile, the incidence rate of brain cancer climbed roughly 30 percent. In the subsequent 24 years, the number of pet cats has increased another 22 percent, to about 93 million. And brain cancer? The incidence rate actually flattened—even decreased slightly according to some reports.

    Over the past 40 years, the population of pet cats has tripled. If there were a causal link between cats and brain cancer, we would expect to see a related increase in incidence of brain cancer. The data do not bear this out. Suggesting otherwise is simply irresponsible.

    Peter J. Wolf
    http://www/voxfelina.com

  5. In that comparison, you need to allow a time lag of at least a decade if not more to account for the long development time of brain cancer. Doesn’t change the lack of association but still. Also, the increase incidence during the 70s and 80s is probably due to better diagnosis.

  6. Alyson

    Maybe its not so much what T. Gondii is doing that is causing the increase in cancer, but what the hosts immune system is doing? (ie; a particularly hostile attack with more inflammation over longer times causing more damage to the tissue, hence more cell turnover hence more chance for a cancer?)

  7. Woodsman

    What difference does it make when it’s already been clearly shown to alter the thinking patterns of humans that this parasite has infested. Causing them to lose an innate sense of concern, fear, doubt, or apprehension that is necessary for their own survival. (Hence, the greatly increased accident rates by T. gondii infected humans.) This is not unlike how it removes a rodent’s fear of cats. Whether that mind will develop or has cancer or not, that parasitized mind is already not functioning like a clear-thinking, soundly-reasoning, common-sense human mind anymore.

    Look at the myriad ways this manifests itself in those who promote TNR programs for cats. Behaving against all common sense and reasoning to ensure those cats spread more of the parasite. Even when they KNOW those cats that they release again will suffer greatly during their shortened lives. Condemning those cats they claim to love to a death by disease, cat-attacks, animal-attacks, starvation, exposure, road-kill, or any other method that they now so-lovingly call “Death by Attrition”. The ways that their cats suffer is clearly defined under all the laws we have for animal-abuse, animal-neglect, cruelty-to-animals, animal-endangerment, and animal-abandonment. Yet somehow they know all this and are aware of it as they do it, but still they cruelly torture cats to show how much they “love” them. This doesn’t even begin to address all the wildlife that they KNOW will suffer horribly under the claws and teeth of those cats, or all the predators that they KNOW will starve to death from their cats destroying all the predators’ food sources. None of this heinous cruelty to animals matters to them. All they know is that THEY MUST DISTRIBUTE MORE T. GONDII REPRODUCTIVE HOSTS WHEREVER THEY CAN, against all reason and sense.

    This clear and blatant contradiction in the minds of cat-lovers who are very likely to be parasitized by Toxoplasma gondii, should be all the proof we need to show how it causes irreversible insanity.

    Toxo being linked to cancer is the least of the problems faced today by this parasite. We are now facing the fact that it is controlling humans to ensure its survival and increased dissemination worldwide through an exponentially-reproducing invasive-species. By making these parasitized humans think that spreading more Toxo-infected invasive-species cats into all native habitats is somehow a good idea. This isn’t just an assault against humans, it’s an assault against the whole food-chain of the world. Cats are capable of annihilating the whole food-chain in every habitat they are found. (They did just that on my own land until I successfully exterminated them all.)

    A parasite that causes humans to spread more cats, and therefor more of the parasite, could very well be humanity’s demise. The collapse of humanity and all other wildlife on this planet, all because of “Awww… look at the cute kitty. Let’s help it.” When in truth they are helping to propagate a parasitized demon in disguise.

  8. Facinating article, Ed, and it drives home the fact that inflammation plays a scary role in cancer; luckily with this knowledge I think there are many things we can do to promote prevention; although I still don’t understand the holdup in finding a cure for this awful disease, brain cancer and other cancers in general. Yes, I know it’s complex, but still. Very sad.

    I knew this post would turn into a war of words about TNR. I won’t get into the silliness of suggesting that cats are some evil power that need to be wiped out; but it’s worth mentioning that:

    1. Cats are not the only animal that carries toxo. All felids, otters, dolphins and even sardines may carry it even if they don’t necessarily spread the disease.

    2. As you pointed out, undercooked meat, also fruit or vegetables, could be a source. According to the University of Cornell, this is a much more likely source of transmission in the United States.

    3. The biggest problem is that most people assume all cats are liberally spreading the disease around. Cats can be given a simple titer test for the disease. And if there are too many to test, that’s the fault of humans, not cats.

    I worked with 2 pregnant veterinary nurses (one worked at a cat shelter, the other a vet clinic) who changed litter boxes every day and never had a problem. Not recommended, but again, the toxo issue is so overblown I felt I had to speak up so those advocating for the mass extermiantion of cats would not use this article to promote their cause. And for TNR advocates, we only need look to the vacuum effect to know why it’s a bad idea anyway.

  9. Eric

    although it is true in general that a mere correlation does not tell the direction of causality (if there is any causality), in this case we know that brain cancer cannot be a major cause of t. gondii infection. This is because the incidence of brain cancer is (fortunately) very low, compared to that of t. gondii infection. In other words, suppose brain cancer incidence to double, from say 10 per 100,000 inhabitants, to 20 per 100,000. But to double t. gondii infections from say 15% to 30%, you’ll have to have 15,000 more infections par 100,000 inhabitants. Those cannot be all brain cancer patients.

  10. Bill Bond

    I have been reading the coments and the Cancer theory is very interesting. I’m 61 years old and have had Toxo all of my life. I never knew I had it until I was 36 yrs. old. I starting having blurring of my vision. My Dr. could not find out what was wrong until he ran a blood test. He told me I have Toxo and refered me to Ohio Stae University here in Columbus, Ohio.
    I was to see a Doctor by the name of Dr. Makely who gave me medicines to help stop the damage and Dialated my Left eye which stayed that way for 4 months until the Toxo ran its course.
    I recovered and about 2 years later I found out that I had another infection. Dr. Makely had passed away during the 2 years and was ref. to Dr. Robert Chambers at Ohio State. He also treated the infection with daraprim and an antibiotic. The daraprim was hard to tolerate but I got through it and recovered again.
    Dr. Chambers felt that I got the Toxo from my Mom from Birth. I hope that this disease is not the cause of Brain cancer!
    I also have concerns if I ever had to take chemo. because of the lowering of my Immune system. What would be the treatment for me and what would be the likely outcome?
    Bill Bond

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