AORTIC 2011, Cairo, Egypt 30 November–2 December 2011

Silica content of home grown maize linked to cancer risk

Professor Vikash Sewram – South African Medical Research Council, Cape Town

I am the Director of the Oncology Research Unit of the South African Medical Research Council, and that’s a parastatal within the South African Government. I also head up the Cancer Research Initiative of South Africa and basically the work that we do encompasses the research that transcends the entire spectrum from early detection of cancer right through to prevention, risk management, as well as the management at end of stage, which is palliation medicine. So we look at how to try to intervene at each stage to help people in the different stages of their cancer progression.

What are the advantages to studying cancer in South Africa?

South Africa indeed is a very heterogeneous population which makes it good to study these population groups and to look at how it’s not just the cultural and lifestyle factors that influence the progression of the disease and the risk profile, but also the genetic make-up and how the genetics of the individual is interacted upon by the environment as well, which plays a huge role. Yes, it is a heterogeneous environment and I think it is a very exciting place to study cancer.

What are you currently researching?

We did a study on oesophageal cancer risk factors in South Africa, which is the largest study to date on oesophageal cancer. There are three regions in the world that are considered world hotspots, one being northern China, the other being Iran, and then there is the Transkei or the former Transkei region of the Eastern Cape Province in South Africa. So the idea is what makes these three regions in the world unique? Why not the rest of the world? What is it that the population in these three groups are doing different to the rest of the world? So this is something that we wanted to unravel. So what we did was we looked at 670 cases of oesophageal cancer within a two year period and we assessed basically the influence of their lifestyle in terms of their smoking, their tobacco usage, the alcohol consumption, their dietary patterns. Also one of the more unique aspects being the use of wild plants as part of the diet, which is very common in indigenous communities, and also the use of traditional medicines. Previously it has never been done this way but we have to take cognisance that the role of traditional healers in this world is becoming more and more popular and there is a lot of recognition in that traditional healers can help. But yet the medicines, so the natural medicines out there, have never been looked at from the perspective of cancer because if you take something that is natural you will realise that there is a problem if there is an acute adverse effect; so if it’s diarrhoea, vomiting and so forth. But if it’s a chronic problem of initiating cancer you will never know until twenty years down the line, by then you will have forgotten that you’ve had the product. We wanted to look at this as well and look at the effect of it.

Basically in a nutshell, in terms of the study, the one thing that’s been consistent is that tobacco, smoking, is indeed a risk factor for oesophageal cancer, and this has been shown time and time again in various international studies. So on that the book is closed, I believe. In terms of alcohol consumption, there have been different perspectives, for example, in our study we have shown that alcohol consumption does increase the risk of developing cancer but in other studies around the world there’s been mixed evidence, but this also goes to talk about a person’s genetic make-up which is why the genetics are as important in that how an individual is able to metabolise the alcohol in their body, and this is influenced by their genetic make-up. So in this population we see that alcohol consumption certainly is an important risk factor.

So given tobacco and alcohol, the government will then ask “But what is the value of your research? How is what you are doing going to influence us in terms of policy and planning?” Because if research is not going to change the course of a disease through policy regulation and planning, then the research that you do is actually meaningless because it is not impacting on the course of the disease. And that is what research should do; it should alter the course of cancer to make things better.  And what we have been able to show is that if we are to remove smoking from this environment you will actually prevent 58% of the cancers, which means that you would get rid of 58% of oesophageal cancers which is a very strong public health message. The other aspect is if we remove alcohol then we would prevent 48% of the cancers. So just alcohol and tobacco smoking itself can actually eradicate half of the oesophageal cancer that we see in the population; so in that sense the very strong public health message to stop the youth to stop smoking and for people to stop consuming alcohol

The other aspect that we have seen is diets. Obviously diets that are rich in fruit and vegetables, sorghum for example, whole wheat, they confer protective effects which means that they will protect you against developing cancer; and that has come through very clearly in our study. Whereas diets that mainly consist of maize, and in the Transkei which is a very rural area, a maize-based diet is the dietary staple but maize also lacks a lot of vitamins that are essential for your daily diet. And so we do see that people that consume a maize-based diet, they have a much higher risk of developing oesophageal cancer.

The other aspects that we explored and I explained to you earlier on is the use of wild plants because people tend to think, well because it grows out there and it is natural, it is safe; but not all that is natural is actually safe because chemicals are everywhere. And although it grows in nature it’s a by product of your plant biochemistry, they still can be harmful to humans. And we have been able to show that there are some plants which are consumed as wild vegetables that are harmful and we have been able to show it in the population and we have added value by actually looking in the laboratory in terms of how these plants are able to mutate DNA. And we know that a mutation in DNA will eventually result in cancer; including some of the traditional medicines that are being used.

So we have looked at the entire spectrum in terms of their lifestyle and their cultural habits as well. One of the novel findings that we’ve had is that there has always been this talk that the maize that is eaten is actually contaminated with a fungus, and this fungus has been shown in various animal studies to have adverse effects in animals. And there have been some studies that have shown to have a risk for cancer but the strength of the studies have always been questionable. Not to say that it’s OK to eat mouldy maize and so forth, it’s not, because it’s an indicator of food quality and naturally we want the population out there to eat healthy food. But the focus has always been, well it is because although the maize could be a contributor, the fungus in the maize. And what we’ve been able to show is that, yes, people who eat home grown maize, because a lot of people out there in this environment are subsistence farmers, so they would grow their own maize and they would eat it rather than buy commercially available products. We have been able to show that, yes, indeed, people that eat home-grown maize are at a risk, however it is not the maize that is actually the risk factor; it’s not the contamination or the mould that has been suspected as the agent responsible for this increased incidence of cancer.

So once again it is intriguing in that here we have a cohort of individuals that consume home-grown maize but it is not the maize itself. So we began to wonder now what could it be, because it is a defined cohort but it is not the maize. So we went further and looked at the way in which they grind their maize, and obviously the way in which they grind on a grindstone results in very fine particles of silica being dislodged from the surface of the stone and getting into the maize. Now you can grind your maize as much as you want to and, together with that, you will grind the silica also. So you find that we have shown, through various experimental techniques that there in the maize that is consumed by these people there are very large particles of silicates that are present; the same kind of silica that you would find, which has been implicated, in a condition known as silicosis which is a lung condition. But these particles get into the lung so you can imagine, even when consumed, these really large particles are actually now being lodged onto the oesophagus. And given that a child starts to eat maize as a dietary staple at a very young age and allow them to continue right to the age of 60, there is this chronic intake of particles. And we know from international studies one of the other causes of oesophageal cancer is chronic inflammation. So if you are continuously subjecting your oesophageal tissue to the very harsh serrated edges of silica over time you are going to have this chronic inflammation, and whilst the body tries to repair itself, you are going to eventually end up with this condition of mutated DNA and the process of carcinogenesis. So we have been able to find that, which is a novel finding and which we have presented at this conference.

So we believe, yes, that is why we’ve seen that people that eat maize-based diets have an increased risk of developing oesophageal cancer but it’s not the mould itself, although I must stress that it is important that people need to know they should not eat mouldy food because it’s not healthy. Food safety is an important aspect and they should also move to healthy foods which includes your fruits, your vegetables and so forth. And also physical activity which also plays a huge role in minimising the burden of cancer.

Could you talk about the Silica study and its aims?

When we did the initial study there was no concept of silica and so forth. We decided to look at what we knew; we had possible risk factors and to determine them in this community. Because a lot of studies were done internationally and some that were done locally were very small studies that really couldn’t measure the impact with a fair degree of statistical certainty. But where we saw this cluster of people that were suddenly consuming maize and were at risk but then further investigation showed that it wasn’t the mould on the maize, then I decided to say, well there must be something about these people that is affecting them. And that’s when the whole concept of maize came in about grinding the maize on a grindstone. And if you look at a grindstone a new one is flat but over time it becomes concave. Then you ask yourself, where does all that silica actually eventually go to? So that was the hypothesis at the time.

So when we went back and we asked the communities to prepare for us how they would prepare maize before consuming it and we had filmed all of this and taken a lot of photos and we asked them then to give us a sample of that maize and then we had them tested. And, as I said, we found really large particle sizes of silica, pure silica, in the maize, obviously unbeknown to people. And, that’s what proved this hypothesis that the maize does actually contain silica and silica could be the other potential source. We now know that people who eat the home-ground maize are exposed to a fairly large amount and fairly large particles sizes of silica. So the next step would be to find the silica in the oesophageal tissue. And that’s what research is, it progresses form one thing to another. So now we are going to go back and we are going to now get the tissue and be able to look at silica. But apart from that there are also biomarkers in blood that can tell you whether a person has been highly exposed to silica, and then we would also evaluate the blood samples of these cancer patients and compare them to non-cancer patients to determine the levels. Because the idea of the research is to prove causality, to prove that exposure to an environmental carcinogen would eventually result in the progression of cancer. So the idea is to actually prove causality, and we are working towards that. First is proof of concept, determine your hypothesis, test your hypothesis, and then to build on that hypothesis to show causality, and that is what we are doing now.