In February 2018, patient advocates Mimi McCord and Maggie Blanks travelled to Kenya for a few days as part of the Cancer Research UK Grand Challenge Mutographs of Cancer project, along with science writer (and former Cancer Research UK blogger) Kat Arney. In this guest post, Kat explains why they went there, and what they discovered about living – and dying – with oesophageal cancer in East Africa.
At its heart, cancer is a genetic disease. Changes in important genes, found in our DNA, cause cells to grow out of control, forming a tumour that eventually spreads around the body.
Some of these changes are inherited, allowing people at high risk to be identified. Others are due to DNA damage caused by our environment and lifestyle. The basis of cancer prevention is to work out what causes these changes, and then find lifesaving ways to prevent cancer from starting in the first place.
Just as the police can narrow down the identity of a criminal by analysing fingerprints left at a crime scene, researchers can now use sophisticated techniques to spot the ‘fingerprints’ left on DNA by harmful agents. These fingerprints are known as mutational signatures.
Right now, we know what causes several of the mutational signatures that have been found so far. Tobacco and UV light are obvious cancer-causing suspects, leaving characteristic trails of destruction in the genome. Others are more elusive.
Led by Professor Mike Stratton and his team at the Wellcome Sanger Institute in Cambridge and Dr Paul Brennan and colleagues at the International Agency for Research on Cancer (IARC) in Lyon, the Mutographs of Cancer is an ambitious Cancer Research UK-funded project mapping the mutational signatures in tumours from 5,000 patients across 5 continents. Their hope is to find new preventable causes of cancer.
The researchers are focusing on 4 types of cancer: pancreatic, kidney, oesophageal and bowel. All are unusually common in certain parts of the world, and all are suspected to have significant preventable causes. The challenge is finding out what they are.
The Mutographs project isn’t a purely scientific venture. Research like this involves people: patients and their families, healthcare professionals and scientists in far-flung locations, donors that fund it and the public that benefit from the findings. So a key part of this project, along with others funded through the Cancer Research UK Grand Challenge, is to include cancer patients and the public. In doing so, the Mutographs team hope to find out more about the experiences of patients in different countries involved in the project and discover how best to engage them and the wider population with the research.
The team recruited two patient advocates to take on this task – Mimi McCord from Heartburn Cancer UK and Maggie Blanks from the Pancreatic Cancer Research Fund. Both women lost their husbands to cancer (oesophageal and pancreatic, respectively) and are passionate about understanding and preventing these diseases for the sake of other families. And in February 2018, they found themselves heading to Eldoret in western Kenya, around 300 km north-west of the capital Nairobi – a region that is plagued by unusually high rates of oesophageal cancer.
Back in 1965, researchers Professor Michael Hutt and Dr Denis Burkitt (who gave his name to Burkitt’s lymphoma) noticed unusually high rates of oesophageal cancer in Uganda and Kenya. Further surveys found a band of unexpectedly high oesophageal cancer incidence stretching through several countries in East Africa and in the eastern parts of South Africa, despite the challenges of gathering accurate statistics and reliable diagnoses.
In fact, there are striking differences in rates of oesophageal cancer across Africa.
The global incidence rate for all types of oesophageal cancer is 9 per 100,000 men and 3.1 per 100,000 women. Based on IARC’s highest quality data, this figure is below 2 per 100,000 men in North African countries like Tunisia, Algeria, and similarly low in West Africa. But rates in East African men are 10 to 20 times higher: 22 per 100,000 in black African men in Zimbabwe and 38 per 100,000 in Blantyre, Malawi. There’s a similar pattern in women, although rates overall are around 30 per cent lower than in men.
Curiously, while most oesophageal cancers in countries like the US and UK are a type called adenocarcinoma, which is associated with heartburn, virtually all the cases in East Africa are a different type, called squamous cell cancers.
Even in wealthier countries like the UK, survival from oesophageal cancer is poor. But the outlook for patients in Kenya is dismal. Many of these cancers are diagnosed at a late stage once a patient is no longer able to eat and has become very frail. This is often because there are multiple cost and time barriers to reaching hospitals or they have spent time seeking help from traditional healers first, so the chances of long-term survival are low.
If a patient can make it to hospital (access to healthcare is very difficult for most people living in rural areas) the most common treatment is surgery followed by the insertion of a tube to keep the oesophagus open, known as a stent, if the patient can afford it.
In rare cases, surgery may be a cure if the cancer hasn’t spread around the body. But although a stent offers an instant improvement in quality-of-life for most people, allowing them to eat and drink again, it can only give them a few months of extra life. But palliative care is scarce, with most hospices only offering day care and limited forms of painkilling morphine, so the end of the journey is likely to be painful too.
As with any type of cancer, prevention is always better than cure. But although the scale of East Africa’s oesophageal cancer epidemic can be seen clearly in hospital statistics and personal stories – one woman we spoke to had lost both her parents to the disease within a few years – there is little known about what’s causing it. This is where the Mutographs project comes in.
The idea of the study is simple: take tumour samples from patients with oesophageal cancer, along with their normal blood cells as a comparison, find out information about the patient’s lifestyle, family history and environment, then analyse the DNA to look for mutational signatures that might reveal the culprit responsible for their disease. But carrying out this kind of research in a country with a comparatively less well-developed healthcare and research infrastructure is challenging.
The IARC team is working with over 25 partners across 5 continents to identify and recruit the 5,000 patients for the Mutographs project. In Kenya, they were able to include a local epidemiological study led by Dr Diana Menya, from Moi University, working in collaboration with Dr Valerie McCormack and Dr Joachim Schuz at IARC.
Their project, called ESCCAPE (Esophageal Squamous Cell Carcinoma African PrEvention research), is a case-control study recruiting oesophageal cancer patients and comparing their environmental and lifestyle factors to the wider population. By working together with Dr Menya and her medical colleagues, the Mutographs team were able to include tumour and blood samples for DNA analysis, and then match them to the information gathered through ESCCAPE.
It’s easy to predict the ‘usual suspects’ linked to squamous cell oesophageal cancer: alcohol and tobacco use are already known to significantly increase the risk. And given that the disease might run in families there may also be an inherited or shared lifestyle component, and results from the Mutographs work should help separate the influence of shared genes from shared environment. But we hadn’t anticipated quite how many other potential risk factors would be out there.
In a rural community outside Eldoret we visited the kitchens of two women, Ann and Emily. These buildings were in the traditional style – a single unventilated room with mud walls and a straw roof – and the ceilings were covered with a thick layer of soot, hanging down in some places like stalactites. Emily was cooking lunch over an open fire housed in a three-part stove. The smoke was overpowering – Mimi managed just 15 seconds before having to dash out for air.
This smoky environment is awash with carcinogenic chemicals called polycyclic aromatic hydrocarbons (PAHs). These chemicals are found in soot and smoke that are released from burning common local fuels such as wood, maize cobs and cow dung. Women, young girls and children are exposed to the highest amounts of PAHs as they spend the most time in the kitchen, often sleeping there at night to keep warm and safe.
There are also personal habits. It’s common in Kenya to drink tea so hot it will scald your mouth – a habit that has been linked with oesophageal cancer in Iran and parts of South America. There may also be an increased cancer risk due to certain vitamin deficiencies in the diet, although evidence is still lacking. Poor dental hygiene could be another factor, as a study in China has shown that the fewer teeth a person has, the greater their risk of oesophageal cancer, but these factors have not yet been studied in Kenya.
Although it’s easy to suspect all these things (and more) as being behind the high oesophageal cancer rates in Kenya, we don’t know how to identify most of these risk factors from the fingerprints that they leave in the genome. And that means we don’t yet know which of them are the most dangerous, or how they might combine together to cause disease.
In many ways, the Mutographs project is the ultimate in cancer prevention research: by finding out exactly what causes DNA damage, we can identify significant specific risk factors and take steps to protect the public.
Right now, the researchers are in the process of collecting patient data and samples. These are sent to IARC in France for processing and the resulting DNA shipped to the Wellcome Sanger Institute for sequencing and analysis.
There’s a lot of work to be done to ensure that the process works from start to finish – for example, checking that enough high-quality DNA can be extracted from the samples for successful analysis – and ensuring that each DNA sample definitely comes from the person on the label. But once the results start coming in, the Mutographs team can start the tricky process of trying to match the mutational fingerprints to the culprits.
While they work on that, the Patient and Public Engagement and Involvement (PPEI) team are thinking about what we should do next. While we were in Kenya we met many people involved in oesophageal cancer treatment and care: Dr Menya and her team, surgeons, palliative care specialists, local dignitaries, and families who had lost loved ones to oesophageal cancer. Unfortunately, we couldn’t speak with any patients, due to their frailty and suffering.
From the people we did speak to, we tried to understand what life was like for patients and their families and what they wanted to see change. Some said there’s a need for more healthcare services in rural areas – so that early detection and appropriate referral are sped up – as well as ways to diagnose oesophageal and other cancers earlier. We’ll be passing this information on to our scientists as they make plans for future research projects.
There’s also a need for more awareness of the symptoms of cancer and ways to reduce the risk. We spent some time talking with a local health minister in the area, Kiprono Chepkok, thinking about how he and his team could use local language radio, community meetings or even phone messaging to spread health awareness and cancer prevention messages.
And once the Mutographs project starts to find preventable causes of oesophageal cancer in the region, we want to know how best to share those findings and support local services to communicate that information to the people who are likely to be affected.
There’s so much more to say about our brief visit to Eldoret and the Mutographs project more widely. We’ll be publishing more stories linked to this post looking in detail at different aspects of cancer in Kenya and around the world, exploring the science behind the project, and discussing the results as they start to come through.