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Oesophageal cancer signatures from around the world

A major global collaboration has provided new insights into the huge variation in oesophageal cancer incidence around the world.

Oesophageal cancer

Oesophageal cancer is the sixth most frequent cause of cancer deaths worldwide. The most common subtype is oesophageal cancer cell carcinoma (ESCC), which affected more than 600,000 people globally last year. The incidence of the disease varies significantly around the world. In fact, it can be more than one hundred times more common in some countries than others. Regions of particularly high incidence include the Golestan province in Iran, the Shanxi province in China and East Africa. High-income countries have a typically lower incidence.  

Epidemiological studies have revealed several potential environmental and lifestyle factors that impact the risk of ESCC. These include tobacco smoking, alcohol consumption, indoor air pollution, contaminated food and drink, very hot beverages, poor diet, poor oral hygiene and opium smoking. Despite improved understanding of the environmental risk factors for ESCC, these factors are still considered insufficient to explain the observed international differences in incidence. It is speculated that an unknown exogenous exposure(s) may be responsible for this.

Identifying mutational signatures

In a recent study, published in Nature Genetics, the Cancer Grand Challenges Mutographs team aimed to understand these international differences by comparing mutational signatures of ESCC genomes from a variety of locations. The team studied 552 cancer genomes from people with ESCC from eight countries. These included countries with high incidences rates (Iran, China, Kenya, Tanzania, and Malawi) and lower incidence rates (Brazil, Japan and the UK).

The team found that despite varying lifestyle and environmental exposures between these countries, the patients’ genomes were surprisingly similar. No mutational signatures could be identified that could account for such high variation in ESCC incidence.

However, the researchers did find associations between specific mutational signatures and some ESCC risk factors, including tobacco, alcohol and opium. These had modest impacts on mutational burden.

Additionally, over 90% of samples carried a mutation in a molecule called APOBEC. This highlights that APOBEC activation is a critical step in ESCC tumour development and may make a subset of tumours more susceptible to certain types of treatment.

This is the first time that experts in mutational signatures and cancer epidemiology have collaborated at such a large scale. This new information has added another piece to the puzzle of ESCC and has opened up new avenues of research.

Professor Sir Mike Stratton, Leader of the Cancer Grand Challenges Mutographs team and Director of the Wellcome Sanger Institute, expressed:

“We’re certain that mutations do contribute to the development and incidence of cancer, but our findings add to a growing body of evidence that some factors drive cancer without necessarily damaging the DNA. We strongly believe a factor does exist to cause such variation in ESCC incidence around the world – one of the ways we’re examining this is to move beyond sequencing cancer genomes and to sequence normal tissue. We’re only now at a position, thanks to recent developments in technologies, that this approach is even possible.”

Image credit: canva

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Cancer / Cancer Research / Genetic Variants