EDITORIAL

Squamous cancer of the oesophagus in Africa: A change of focus for research

Squamous cancer of the oesophagus (SCCO) continues to be a major problem in many parts of East, Central and southern Africa. In 2005, the fruitless nature of the search for a single potent carcinogen responsible for high regional incidences of SCCO was noted.^[1]

Research effort continues to be expended on case-control studies, on meta-analyses, and on systematic reviews of these studies, still with nothing essentially new to report: tobacco, alcohol, and nutritional deficiencies remain important^[2-4] Polycyclic aromatic hydrocarbons (PAHs) currently receive regular mention, and many other substances are mentioned in each litany of possible causes,^[4-6] none with compelling evidence against them as major factors.^[7] Genetic studies have been helpful but not ground-breaking in the move to understand endemic SCCO.^[4]

Tobacco, alcohol, PAHs, genetic differences - none of these can logically be the key factor causing the very high incidences of SCCO in some communities, compared with communities that are similarly exposed but have incidences of a lower order of magnitude. They are important, but the evidence so far suggests that they are peripheral to the main reasons behind endemic incidences. In susceptible communities, case-control studies may help to identify reasons for individual cases of SCCO, but do not address community susceptibility.^[8,9] This approach of using case-control comparison has been exhaustive and is now producing little in the way of new information. The existence of a single undiscovered potent carcinogen or combination of carcinogens that will be uncovered by case-control study should now be accepted as extremely unlikely. A promising line of research into mechanisms of oesophageal squamous carcinogenesis has opened up with the naming of non-acid reflux as having a strong and probably causative association with SCCO^[10] - in contradistinction to the known association of acid reflux with oesophageal adenocarcinoma.

Is it not now time for two changes of focus: firstly to return to the problem of community susceptibility as repeatedly addressed by Van Rensburg,^[11,12] rather than individual susceptibility? Comparative study of communities rather than of individuals should clarify reasons for some communities being more susceptible than others.

A second change of focus is to consider factors other than carcinogens, but which predispose to carcinogenesis. Van Rensburg^[11] stated in 1981 that the choice of cereal that constitutes the bulk of the diet in those adhering to a simple lifestyle is the main determinant of risk. In Africa, risk is invariably associated with maize. He has maintained that nutritional deficiency is the comprehensive cause of endemic levels of SCCO, and advocates prevention by healthy nutrition that includes all the necessary micronutrients from a young age. Sammon and colleagues^[7,9,13] have in addition identified evidence that in communities that depend on maize, there is a strong association with maize meal; the rapid release of free fatty acid starting from the time of milling of maize combines with nutritional deficiency to create population susceptibility. Prevention requires elimination or mitigation of the risk associated with chemical degeneration of maize meal,^[9] combined with a diet containing all necessary vitamins and micronutrients.

It is now prudent to abandon the search for an undiscovered potent carcinogen and to address community susceptibility in endemic areas, acknowledging that currently we have no credible candidates for predisposition apart from nutritional deficiencies of a maize-based diet, and chemical degeneration of milled maize. Region-to-region and community-to-community comparisons are appropriate.

Investigation of causal links between SCCO, non-acid reflux, and diet currently offers some promise of explaining mechanisms of predisposition to carcinogenesis.

There is now sufficient evidence to expand the implementation of preventive measures: targeted supplementation of maize meal in countries where this has not yet been enforced, and recognition that maize meal is a rapidly perishable food that requires control of chemical content at point of sale.

Alastair M Sammon, Eugene J Ndebia

Department of Human Biology, Faculty of Health Sciences, Walter Sisulu University, Mthatha, Eastern Cape, South Africa alastair.sammon@gmail.com

References

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2. Sewram V, Sitas F, O'Connell D, Myers J. Diet and esophageal cancer risk in the Eastern Cape of South Africa. Nutr Cancer 2014;66(5):791-799. https://doi.org/10.1080/01635581.2014.916321        [ Links ]

3. Kachala R. Systematic review: Epidemiology of oesophageal cancer in SubSaharan Africa. Malawi Med J 2010;22(3):65-70. https://doi.org/10.4314/mmj.v22i3.62190        [ Links ]

4. Asombang AA, Chishinga N, Nkhoma A, et al. Systematic review and meta-analysis of esophageal cancer in Africa: Epidemiology, risk factors, management and outcomes. World J Gastroenterol 2019;25(31):4512-4533. https://doi.org/10.3748/wjg.v25.i31.4512        [ Links ]

5. Patel K, Wakhisi J, Mining S, Mwangi A, Patel R. Esophageal cancer, the topmost cancer at MTRH in the Rift Valley, Kenya, and its potential risk factors. Int Sch Res Notices 2013;2013: Article ID 503249. https://doi.org/10.1155/2013/503249        [ Links ]

6. McCormack VA, Menya D, Munishi MO, et al. Informing etiologic research priorities for squamous cell esophageal cancer in Africa: A review of setting-specific exposures to known and putative risk factors. Int J Cancer 2017;140(2):259-271. https://doi.org/10.1002/ijc.30292        [ Links ]

7. Sammon AM, Ndebia E. Aetiology of oesophageal cancer in Africa - a review of historical and current evidence. Glob J Health Sci 2019;11(12):91-108 https://doi.org/10.5539/gjhs.v11n12p91        [ Links ]

8. Rose G. Sick individuals and sick populations. Int J Epidemiol 2001;30(3):427-432. https://doi.org/10.1093/ije/30.3.427        [ Links ]

9. Sammon AM. Cancer of the oesophagus in Africa, population susceptibility, and preventive intervention. Glob J Health Sci 2021;13(3):124-137. https://doi.org/10.5539/gjhs.v13n3p124        [ Links ]

10. Uno K, Iijima K, Hatta W, et al. Direct measurement of gastroesophageal reflux episodes in patients with squamous cell cancer by 24-h pH-impedance monitoring. Am J Gastroenterol 2011;106(11):1923-1929. https://doiorg/10.1038/ajg.2011.282        [ Links ]

11. Van Rensburg SJ. Epidemiologic and dietary evidence for a specific nutritional predisposition to esophageal cancer. J Natl Cancer Inst 1981;67(2):243-251.         [ Links ]

12. Van Rensburg SJ, van Rensburg SJ. Esophageal squamous cell cancer susceptibility: Environmental and nutritional associations reveal a universally applicable pathogenesis scenario (Review). World Acad Sci J 2019;1(5):219-228. https://doi.org/10.3892/wasj.2019.24        [ Links ]

13. Sammon AM, Iputo JE. Maize meal predisposes to endemic squamous cancer of the esophagus in Africa: Breakdown of esterified linoleic acid to the free form in stored meal leads to increased intragastric PGE2 production and a low-acid reflux. Med Hypotheses 2006;67(6):1430-1435. https://doi.org/10.1016/j.mehy.2006.05.037        [ Links ]