Mystery of the environmental triggers for cancer deepens

One of Britain's top cancer experts said last week that scientists will need to reconsider how environmental triggers can cause tumours to form or develop. Michael Stratton is the director of Wellcome Sanger Institute. He said that recent findings from an international research study on cancer which sought to identify environmental triggers in oeosophageal carcinoma showed that current scientific knowledge of tumor formation was lacking.
Research on an oesophageal carcinoma type was done to discover why certain areas of the globe have high rates. These are areas in Iran, Turkey and Kenya where the disease is most prevalent. It is also very rare in other parts of the globe.

Stratton said that there are many external factors that could explain the high rates. For example, some researchers suggest that high alcohol intake may be a factor. Iran is very low in alcohol consumption. Others suggested that oil fumes could be involved from cooking. These high rates are not explained by any common factor. This has been a puzzle.

To help solve the mystery, Stratton was awarded 20m by Cancer Grand Challenges, an initiative launched by Cancer Research UK (UK) and the National Cancer Institute (USA). His group now studies the genomes for several types of cancer, and work on oesophageal-squamous carcinoma is being done with this funding.

It can be difficult to treat oesophageal carcinoma because it is often diagnosed long after the tumour has formed inside a person's throat. Kenya has a high rate of this disease. Because of the stigma attached to cancer in Kenya, many patients don't go straight to hospitals or doctors. Mimi McCord, who was involved in the study as a patient advocate, stated that patients often seek help from faith healers and herbalists.

As their symptoms worsen, relatives bring them to central hospitals across the country. Most of them die by then.

Image intensifiers are used to perform esophageal surgery. Photograph by BSIP/Universal Images Group/Getty Images

Scientists began to collect tumour tissue and blood from people affected by oesophageal carcinomas in order to pinpoint their environmental triggers. Paul Brennan from the International Agency for Research on Cancer, Lyon, France, who was also part of the project, stated that we took samples from hundreds of people in Iran, Kenya, and other countries. Each individual provided a sample of their tumor and their blood.

Researchers used this information to search for mutations in the genome of tumours. A mutational signature refers to a specific pattern of mutations found in DNA of certain cancers, such as skin and lung cancers. Stratton explained to the Observer that lung cancer is caused by smoking, while skin cancer is triggered in part by ultraviolet radiation from sunlight.

It is possible to look at a cancer's genome and see the mutational signatures. This can give you a good idea of how it was caused.

The CRUK study had the goal of identifying a similar mutational signature in oesophageal carcinoma. This would have led to an environmental explanation for high rates of the disease in Kenya and other countries. To their great surprise, scientists could not find any signatures that would indicate that a chemical or another factor caused the mutations that lead to a cancerous oesophageal cells.

This is a setback because if we had discovered a distinct mutational signature, then we would have been able make hypotheses about the cause. For example, in the diets and habits of high oesophageal carcinoma rates, said Stratton. Then we would have been able to identify the problem and provide public health solutions. Unfortunately, we are still unable to do this.

The Nature Genetics study published last week by Stratton suggests that scientists will need to look at more factors that can cause cancer.

External factors can cause oesophageal-squamous carcinoma, but not directly. We have also found evidence that chemicals may be capable of working in other ways than directly causing mutations. This could increase the chances of someone developing cancer. This is the message that this animal experiment backed study should convey. It will be necessary to reconsider our assumptions about how certain cancers are developed. This is a critical lesson.