Oesophageal cancer is the fourth most commonly diagnosed cancer and a major cause of cancer morbidity and mortality in Kenya. It is an aggressive cancer with poor outcomes in part due to late-stage diagnosis, with patients presenting with inability to eat, weight loss and pain in the throat. Kenya lies on the African “oesophageal corridor”, a region beginning from the north-eastern part of the continent to southern Africa, which have high incidences of the disease. While the geographical zones, ethnic groups and cultural practices in these high-risk areas are widely varied, it is speculated that unknown exogenous exposure(s) could be responsible for the higher disease burden in this corridor.

Histologically, the most common subtype of oesophageal cancer in Kenya is the oesophageal squamous cell carcinoma (ESCC). While we have not determined the genesis of ESCC, a variety of risk factors have been put forth to explain this disease. Among them include tobacco smoking and alcohol consumption, which have been shown to act synergistically to increase the risk of ESCC. The consumption of hot beverages, a common practice in many regions of Kenyan highlands, is an added risk. Furthermore, exposure to polycyclic aromatic hydrocarbons from indoor air pollution and nyama choma, aflatoxin- and mycotoxin-contaminated food and drinks have also been associated with increased risk of oesophageal cancer.

As we age, our genome is under assault from a number of DNA damaging agents that can result in changes in the DNA sequence, collectively known as mutations. These mutations, if not repaired, accumulate over time, and remain imprinted into the genome of the affected cells. Subsequently, new  daughter cells generated from these affected cells retain a historical archive of these mutagenic exposures. These mutagenic processes and agents have been shown to produce characteristic patterns of DNA lesions for a given mutagen (or mutational process) referred to as a mutational signature or pattern. Exposure to different carcinogens including UV light, aflatoxins, mycotoxins, arsenic, and smoking produce very specific mutation fingerprints in our genome.

The goal of mapping these mutation fingerprints is to not only understand the carcinogenic process, but also pinpoint etiological agents, especially when epidemiological studies fail to show specific risk factors. For example, in some oesophageal cancer studies there are reports of mutation fingerprints related to alcohol consumption. Therefore, is it possible to identify other unique mutation patterns from other oesophageal carcinogens? Can these signatures tell us the life history of oesophageal cancer patients through the genomic fingerprints of past exposures? Can we use these unique mutational fingerprints to identify causative agents in oesophageal cancer hotspots like Bomet, Meru and Marsabit? While there are on-going and past studies addressing these questions, relatively low sample numbers (68 in one concluded study) and good quality samples hindered robust results.

The advent of next generation sequencing has ramped up cancer research, and many cancers whole genomes sequenced. However, genomes from patients of African descent remain understudied and under sequenced. Despite Africa having 15-20% of the world’s population, and a reported widest genetic variation of any continent, only 2% of the genetic sequencing and information have been completed on African cancers. With evidence showing significant inter-ancestral differences in cancer cell phenotypes and molecular alterations that drive cancers, a move to enhance whole genome sequencing of all cancers would not only benefit etiological studies, but also studies to advance knowledge on clinical applications in different populations.

The potential use of mutational fingerprints in identification of cancer-causing agents is an exciting area of research. Scientists ‘playing detectives’ by uncovering the evidence left behind by carcinogens would have  a great impact in the understanding of mechanisms of carcinogenesis and will be instrumental in identifying the causes of geographical variation in incidence rates of cancers like ESCC. While studies have shown that known carcinogens like arsenic and acetaldehyde are present in water and brews in high incident areas like Marsabit and Bomet, being able to directly link these chemicals to formation of tumours will have a stronger influence in government policy on preventative measures and in educating the public about potential ways to reduce the risk of getting this cancer.