Skip to main content

Factors associated with the high prevalence of oesophageal cancer in Western Kenya: a review

Abstract

Oesophageal carcinoma (OC) is highly prevalent in Western Kenya especially among the members of the Kalenjin community who reside in the Northern and Southern areas of the Rift Valley. Previous authors have suggested potential association of environmental and genetic risk factors with this high prevalence. The environmental factors that have been suggested include contamination of food by mycotoxins and/or pesticides, consumption of traditional alcohol (locally referred to “Busaa” and “Chan’gaa”), use of fermented milk (“Mursik”), poor diet, tobacco use and genetic predisposition. The aim of this paper is to critically examine the potential contribution of each of the factors that have been postulated to be associated with the high prevalence of the disease in order to establish the most likely cause. We have done this by analyzing the trends, characteristics and behaviours that are specifically unique in the region, and corroborated this with the available literature.

From our findings, the most plausible cause of the high incidence of OC among the Kalenjin community is mycotoxins, particularly fumonisins from the food chain resulting from poor handling of cereals; particularly maize combined with traditional alcohol laced with the toxins interacting synergistically with other high-risk factors such as dietary deficiencies associated alcoholism and viral infections, especially HPV. Urgent mitigating strategies should be developed in order to minimize the levels of mycotoxins in the food chain.

Background

Oesophageal carcinoma (OC) is the sixth cause of cancer related mortality, and the eighth most common cancer globally. It is more common among men, and associated with older age [1,2,3]. There are two histological types; oesophageal adenocarcinoma (OAC) which presents in the lower part of the oesophagus, and oesophageal squamous-cell carcinoma (OSCC) which tends to be on the upper and middle part, and arises from epithelial cells that line the oesophagus [4,5,6,7,8]. Several predisposing risk factors for OC have been reported [9,10,11]. The risk factors that have been reported for OSCC include tobacco smoking and consumption of alcohol [12,13,14], consumption of hot food and beverages [15,16,17,18], including “Mate”, a tea-like nonalcoholic infusion from Ilex paraguariensis plant [19, 20] and poor diet [10]. The main risk factors that have been reported to predispose OAC include gastroesophageal reflux disease, obesity, smoking, aging, diet and radiation therapy [5, 14, 21,22,23,24]. Factors known to protect against adenocarcinoma development include Helicobacter pylori infection, a diet rich in fruits and vegetables, and use of aspirin and other non-steroidal anti-inflammatory agents [10, 25, 26]. The role of human papilloma virus (HPV), an oncogenic virus is still debatable [27]. Some researchers have concluded that it may have a role in the OSCC carcinogenesis based on meta-analytic reviews [28,29,30], while others have concluded that it has no direct role [31,32,33]. Authors from a recent publication have also provided evidence of the lack of HPV association based on molecular biology criteria [34]. In addition, recent genomic studies obtained from sequencing OSCC samples collected from sub-Saharan Africa (SSA), suggest that the endemic nature of the disease is due exposure to a carcinogen other than tobacco and oncogenic viruses [35].

The incidences vary globally, with OAC being more prevalent in developed world; and OSCC in low and middle income countries (LMICs) with Eastern and Southern Africa, as well as Eastern Asia recording the highest prevalence [1, 8, 14, 36,37,38]. It has also been reported to be more prevalent in black men [39,40,41]. This has largely been attributed to poor diet/dietary deficiencies, alcohol consumption and tobacco smoking, exposure to mycotoxin metabolites (aflatoxins and fumonisins in particular) and HPV infection, especially in SSA [37, 42,43,44,45]. Interestingly, authors from a fairly recent research paper have reported the age-standardized incidence rates of OSCC in East Africa to be higher than the mean world rates, suggesting that the incidence in the region may be higher than initially postulated [46]. Currently, it is difficult to get accurate national data on the prevalence of OC in Kenya because there only two cancer registries, one based in the capital Nairobi (Nairobi Cancer Registry [NCR]) and the other in Eldoret (Eldoret Cancer Registry) which is located in the Western region respectively [47, 48]. Data from NCR have reported OC to be the second most diagnosed cancer in men (8.9%) after prostate, and third in women (4.9%), after breast and cervical [49]. A new report from NCR classifying cancer risk as per ethnic group still has OC as the third most frequent [50].

However, OSCC has been reported to occur more frequently in Western Kenya, and more significantly among the members of the Kalenjin community who reside in the Northern and Southern areas of the Rift Valley [51,52,53,54,55,56,57,58]. Five-year data from Eldoret Cancer Registry regarding cancer prevalence in Uasin Gishu County, an area resided mainly by the Kalenjins shows OC to be the most common cancer. It is most prevalent among men followed by leukemia and prostate, whereas it is third most common in women after cervix and breast [48]. It has been reported to literally occur in all the age groups, with OSCC situated at the middle third portion of the oesophagus being the commonest histological type [53, 54, 56, 57, 59]. Previous authors have suggested potential association of environmental and genetic risk factors with this high prevalence. The environmental factors that have been suggested include consumption of traditional alcohol (locally referred to “Busaa” and “Chan’gaa”), use of fermented milk (“Mursik”), poor diet and exposure to mycotoxins and nitrosamines [37, 54, 57, 60,61,62].

The North and Southern parts of Rift Valley comprise an important agricultural area in Kenya. Indeed, it has been dubbed at the “bread basket” of the country. The Kalenjin constitute the largest community residing in the region, with Kalenjin sub-tribes of Nandi, Keiyo and Marakwet living in the northern part; while the Kipsigis and their Maasai cousins residing in the southern part. The Luhya community is mainly found in the neighbouring region (formerly referred to as Western Province), and some parts of the North rift. Naturally, the main activity in the region is farming, in both small and large scales. A type of stiff porridge made by mixing cornmeal with boiling water, commonly referred to as “Ugali” is the most popular dish in the area; and is mainly consumed with vegetables, and occasionally meat for those who can afford [63, 64]. This is usually combined with milk, either fresh or fermented (“Mursik”) among the Kalenjin [65]. Alcoholism is rampant especially in the rural areas, with the most popular drink being traditional brews, either “Busaa” or “Chan’gaa” [66, 67]. Incidentally, this is the region that unusually bears one of the highest brunts of OC in the world, especially among the Kalenjin community [46, 48, 52,53,54, 57, 58]. We have critically examined the potential contribution of each of the factors that have been postulated to be associated with the high prevalence of the disease in order to establish the most likely cause. We did this by analyzing the trends, characteristics and behaviours that are specifically unique in the region, and corroborated this with the available literature. These include the roles of contamination of food by mycotoxins and/or pesticides, consumption of traditional alcoholic brews and “Mursik”, tobacco use, genetic predisposition and HPV infection.

Mycotoxins

Mycotoxins are toxic metabolites produced by fungi that normally contaminate agricultural cereals, either in the field, during harvest or storage; and are mainly associated with cereal crops, including maize, wheat, barley, rice and oats. They are common throughout the world, and mycotoxin contamination of food is now considered a serious public health problem, especially in SSA [68, 69]. They include aflatoxins, fumonisins, zearalenone, moniliformin, ochratoxins, trichothecenes, deoxynivalenol, diacetoxyscirpenol, and nivalenol [43, 70, 71]. Aspergillus flavus and Aspergillus parasiticus which are abundant in warm and humid regions are the main aflatoxin producing group of fungi, whereas fumonisins and trichothecenes are mainly produced by Fusarium verticillioides and F. proliferatum [45, 72,73,74]. Mycotoxins metabolites have been associated with the development of several diseases including aflatoxicosis, hepatotoxicity, neural tube defects, immunosuppression, infertility, haematotoxicity, growth impairment and cancer [74,75,76,77,78]. The metabolites that have been described to induce oncogenesis include fumonisins and aflatoxins, which have both been associated with the development of oesophageal and hepatocellular carcinoma [HCC] [79]. Most of the current publications however tend to associate aflatoxins more with HCC, whereas fumonisins are linked to the development of both malignancies [80,81,82,83]. Additionally, fumonisins have been associated with renal carcinoma [84, 85].

Fumonisins

Fumonisin B1 (FB1) is the most prevalent member of fumonisin family of toxins, and its link to the development of OC has been known for a long time; having been implicated in the high incidence of OC in China and South Africa in the 90s [76, 81, 86,87,88]. It is also a known hepatocarcinogen that causes HCC [82, 83, 87,88,89]. The mechanisms for carcinogenesis are still uncertain. It is however thought to be nongenotoxic (non-DNA reactive), and several mechanisms have been postulated for its oncogenesis. These include possible role of oxidative damage during initiation and disruption of lipid metabolism, integrity of cellular membranes and altered growth-regulatory responses [78, 83, 88]. FB1 has been demonstrated to be nongenotoxic in bacterial mutagenesis screens or unscheduled DNA-synthesis assays [84, 90]. Previous researchers have concluded that it produces oncogenesis through apoptotic necrosis, atrophy, and consequent regeneration as a result of ceramide synthase inhibition and disruption of sphingolipid metabolism [82,83,84, 90,91,92]. FB1 bears a structural similarity to the cellular sphingolipids, thereby disturbing the metabolism of sphingolipids by inhibiting ceramide synthase enzyme leading to accumulation of sphinganine in some cells and tissues thus inducing apoptosis, especially in the liver cells. The ability of FB1 to accumulate sphingosine or sphinganine and arrest the cell cycle in selected cells is thought to play an important role in the carcinogenesis or disease [78, 88, 93].

Aflatoxins

Aflatoxins are known human carcinogens that have been demonstrated to participate in the pathogenesis of HCC, with aflatoxin B1 (AFB1) being the most dominant and potent aflatoxinin [80, 81, 94, 95]. AFB1 in conjunction with hepatitis B virus has been associated with the development of HCC in resource limited countries [72, 85, 96,97,98,99,100]. In addition, the toxic effects of aflatoxins on immunity and nutrition combine to negatively affect health factors including HIV infection which accounts for a high percentage of the burden of disease in developing countries [80, 94]. Indeed, the dietary exposure to aflatoxins has been touted as an important contributor to the high incidence of HCC in Asia and SSA, where almost 82% of the worldwide cases occur [97, 101,102,103]. The exact mechanism is not yet very clear, but it is thought to be through conversion of aflatoxin B1 to aflatoxin B1 formaminopyrimidine, a mutagenic and carcinogenic adduct metabolite that acts synergistically hepatitis B virus to generate mutations of the tumour suppressor genes thus resulting in hepatocellular carcinoma [104,105,106,107,108]. Additionally, aflatoxin contamination has also been described as risk factor for esophageal cancer [109].

Mycotoxin contamination

There are many published reports about mycotoxin contamination, and its toxic metabolites in Kenyan cereals, particularly maize [60, 61, 110,111,112,113,114,115,116,117]; including outbreaks [118,119,120]. This has largely been associated with delayed and poor harvesting methods, drying and storage in deficient or inappropriate facilities [115, 116, 119, 121, 122]. Mycotoxins have also been detected in food including meat, milk and eggs; as well as in traditional beer. This has been attributed to contaminated livestock feeds and maize flour used in the fermentation of “Busaa” [123, 124].

Taking Uasin Gishu County in the North Rift as a case in point, the rise in mycotoxin contamination, can be historically traced to failed agricultural policies and diminishing Government support over the years [125, 126]. The Kalenjin are pastoral by nature, but during the colonial period (up to late1950s), they like every other indigenous Africans were confined to tribal homelands commonly referred to as “reserves”, where they practiced peasant farming. They grew finger millet and maize (“Cheborosinik”) introduced earlier by the British & Portuguese, that was just enough for subsistence, and supplemented with dairy products [63, 65, 127, 128]. The maize was well dried and stored in small barns, thereby exposing the cereal to very low levels of contamination [129,130,131,132]. After Independence (1961-1976), land was distributed and the farmers adopted higher yielding varieties of maize and wheat which led to a significant increase in agricultural production. The cereals were marketed by a farmer’s organization named the Kenya Farmers Association (KFA) under strict regulations by both the Ministry of Agriculture and Maize and Produce Board [125, 126]. The farmers were also cushioned by a seasonal credit insurance system (Guaranteed Minimum Returns), in case of any crop failures mainly due changing weather patterns. There was therefore little contamination, or the contaminated products were destroyed before reaching the market [127, 133, 134].

Since the introduction of liberalization of maize produce in 1987/88, farmers have had to endure with a lot of challenges including deregulation of prices, low producer prices, low quality inputs, weather variability, elimination of subsidies, disincentives for production, including inefficiencies in marketing, reduction in the acreage and several other problems [122, 126, 134, 135]. In addition, there has been significant importation of cheap maize over the years, thus dampening the local prices. The ever-changing weather pattern and lack of storage facilities coupled with the high cost of drying has exacerbated the problem. This has led to poverty and poor management of the crop, with farmers adopting poor methods of handling the produce in order to decrease the costs of production. The farmers now tend to dry their maize in open spaces in urban areas when rejected by the millers due to high moisture content, whereby they may not salvage in an event of a sudden downpour, thus exposing the grain to further contamination [136] (Fig. 1 ). In addition, the rotten pieces are no longer discarded but are either converted to animal feeds or milled and sold to “Busaa” brewers [123, 125, 137,138,139]. This directly introduces mycotoxins to the food chain, either through consumption of “Ugali” and milk (both staple diets among the Kalenjin), meat, eggs and other animal products as well as “Busaa” [60, 123, 124]. This is evinced by the reports from the region of unacceptably high levels of mycotoxins and its metabolites in stored maize [61, 110,111,112], and more disturbingly, including milled maize samples [60]. In some instances, the extent of contamination is so high that sorting the harvested maize to remove those with moulds did not reduce the mycotoxin content [114]. High levels of aflatoxin contamination have even been detected in human serum, and this has been correlated with the level of poverty [140, 141]. With regards to “Busaa”, a very popular traditional drink in the region [66], it is apparent that the content of mycotoxin and its metabolites would be high in most samples, based on the rampant use of flour from rotten maize for fermentation. Studies conducted in the region have reported as such [124, 139]. However, related studies have reported that commercial beer have very low mycotoxin toxicity confirming the fact that the farmers tend to supply millers with clean maize because of stringent requirements by the millers, but select the rotten pieces to be sold to “Busaa” brewers who are not regulated by authorities [137, 142]. We hypothesize that mycotoxin (especially fumonisin type) contamination of food and alcohol is one of the most likely causes of the high prevalence rates of oesophageal, hepatic and related cancers in Western Kenya.

Fig. 1
figure 1

Drying maize in the open

Alcohol consumption and tobacco smoking

The association between consumption of alcohol and tobacco smoking with the development of OC, especially OSCC has been known for a long time [13, 23, 143,144,145]. Indeed, they have both been listed as major contributors of OSCC in SSA [42]. They are thought to interact synergistically in the development of OC, and some researchers have even reported a 35-fold increase in the risk resulting combined use of alcohol, tobacco and marijuana [146,147,148,149]; and up to 50-fold in heavy smokers and drinkers compared to those who do not drink or smoke [13].

The pathophysiology of alcohol in OSCC is believed to involve acetaldehyde, a toxic ethanol metabolite which is a recognized carcinogen. In addition, ethanol itself stimulates carcinogenesis by inhibiting DNA methylation and by interacting with retinoid metabolism [150,151,152]. Polymorphisms involving alcohol and aldehyde dehydrogenase, the enzymes that metabolize ethanol have therefore been associated with increased risk. The genotypes that have been identified from several studies are alcohol dehydrogenase-1B (encoded by the ADH1B gene) and aldehyde dehydrogenase-2 (encoded by ALDH2) respectively. Carriers of these polymorphic genes are discouraged from taking alcohol based on studies conducted in Asia [153,154,155,156,157,158]. To date there is scant information from the literature about related genetic studies that have been conducted on Africans; despite the reportedly higher prevalence on OSCC among African-Americans, especially those who use alcohol and tobacco [39, 40]. Combination of tobacco and alcohol consumption further increases the risk of OSCC [146, 147, 159, 160]. The molecular mechanisms by which tobacco induces cancer is postulated to be mediated through the exposure of tobacco-specific carcinogenic nitrosamines; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine [NNN] [161]. NNK and NNN initiate tumours through a two-fold synergistic process; deleterious mutations in oncogenes and tumor suppression genes resulting in DNA adducts, as well as enhancement of the tumour growth. The nitrosamines promote tumour growth by binding to the nicotinic acetylcholine receptors and stimulating the deregulation of cell proliferation, survival, migration and invasion which provides an enabling environment for the proliferation [161,162,163,164].

Members of the Kalenjin community are not heavy tobacco smokers, but their rampant consumption of traditional alcohol (“Busaa” and “Chan’gaa”) laced with mycotoxins could be a potential trigger of OSCC.

Traditional fermented milk (“Mursik”)

Fermented milk is part and parcel of Kalenjin culture, and is usually drunk after every meal. Some have even hypothesized that their world-class athletic prowess is associated with the use of “Mursik” [165]. Its preparation process involves the use of a gourd (“Sotet”), a bow shaped stick (“Sosiot”) usually from palm trees and charcoal from selected trees and shrubs (“Suteiywo”), the commonest being Senna didymobotrya, Juniperus procera, Plectranthus barbatus, Olea europaea and wattle trees. The sticks are used to grind embers of the charcoal by pressing against the walls of a gourd in a methodical, circular in and out movement of the hand until the inside of the gourd is evenly covered with fine dust. Boiled milk is then poured into the gourd and allowed to ferment in cool dry conditions. If a new gourd is used, then it has to be first “sweetened” in order remove the bitter taste. This is done by the use of fresh bark from either Ozoroa insignis, Pappea capensis or Ficus thonningii. The bark is placed inside the gourd which is then filled with water and left to cure for three days [166].

The association of fermented milk including “Mursik” with oncogenesis is inconclusive [167,168,169,170,171,172]. From the literature, the publications that link this mainly relate to presence of acetaldehyde, a carcinogenic substance in sour milk and other contaminants as a result of poor processing [62, 173,174,175]. Indeed, most of the publications correlating the prevalence in OSCC among the Kalenjin community to the consumption of “Mursik” have postulated as such, but there is no direct relationship from literature [54, 58, 62]. In any case, the amount of acetaldehyde from fermented milk may not be as high as the amount from alcohol per se. The most plausible association between “Mursik” with OSCC would therefore emanate from “Mursik” containing mycotoxins originating from contaminated animal feeds; which would act synergistically with acetaldehyde present in the fermented milk [60, 70, 123, 124, 138, 176]. Further research should be conducted to determine the levels of mycotoxins and aldehydes in “Mursik”.

Pesticides and herbicides

Being an agricultural region, there is widespread use of pesticides and herbicides in the Rift Valley. From the literature, there are several publications linking the use of these chemicals with potential development of several types of cancers [177,178,179]. Most of these reports however are based on anecdotal evidence and are largely inconclusive, often requiring more studies for definitive conclusions [180,181,182,183,184,185,186]. Nevertheless, most of the research that has been conducted to date have reported the absence of association between pesticide use and OC [187,188,189]. Of note however, is a report by some researchers about a statistical correlation between pesticide use among agricultural workers and development of some forms of cancer later on in life, including OSCC [190].

Genetic predisposition

To date, there is no specific gene that has been specifically identified whose overexpression will lead to development of OC, although many genes and miRNAs including p53, VEGF, cyclin D1, and miR-21 are considered useful when predicting the prognosis of EC [191,192,193,194]. The predisposition to OSCC is mainly associated with life style risk factors including smoking and alcohol use, and specifically on the polymorphisms in the enzymes involved in metabolism of alcohol acting synergistically with nitrosamines from exposure to tobacco [146, 150, 155, 195]. Genetic polymorphisms of the genes encoding alcohol dehydrogenase-1B (ADH1B), aldehyde dehydrogenase-2 (ALDH2) and cytochrome P4502E1 (CYP2E1) are known to affect the metabolism of alcohol among the Asian populations [153, 154, 158, 196,197,198]. Indeed, polymorphism in ADH1B and ALDH2 in combination with tobacco by-products have been demonstrated to increase the risk of OSCC by up to 190 times in Japanese population, and predisposition to OSCC [160]. Carriers of these polymorphic genes are therefore discouraged from taking alcohol [10, 156, 159]. Unfortunately, there is scant information from the literature about studies on the impact of these polymorphisms among the Africans despite the reportedly, unusually high incidents of OSCC among the African-American users of alcohol compared to other races [39, 40].

Human Papillomavirus Infection

HPV infection has for a long time been postulated to be a potential causative agent in the etiology of OC [199]. Despite the fact the hypothesis regarding the link has been controversial and inconclusive [32, 33, 200, 201], there are several reports to date associating the etiology of OC with HPV virus [27, 202,203,204,205,206], especially in high incidence geographical regions [30, 207,208,209,210,211]. The mechanism of oncogenesis has is thought to be through the inactivation of tumour suppressor genes. HPV, particularly 16 and 18 subtypes has been described to interact with p53 and Rb tumour suppressor proteins leading to their loss of function. In addition, HPV-16 E6 has been demonstrated to down-regulate miR-125b, thus activating the Wnt/beta-catenin signaling pathway which promotes tumorigenesis [212, 213]. Despite the Kenya being in the HPV high risk geographical region, results from a research conducted from samples collected in MTRH suggest that HPV may not play a role in the pathogenesis of OSCC [214]. However, we cannot completely rule out the role of HPV on the oncogenesis of OSCC in the region.

Conclusions

The most plausible cause of the high incidence of oesophageal cancer in Western Kenya, especially among the Kalenjin community is mycotoxins, particularly fumonisins from the food chain combined with traditional alcohol laced with the toxins interacting synergistically with other high-risk factors such as dietary deficiencies associated alcoholism. Genetic predisposition and HPV-infection may also contribute. , Further research (including population-based case-control studies) should be undertaken to establish their roles. Attempts should be made by the regulatory authorities to eliminate or minimize the levels of mycotoxins in the food chain. Urgent mitigating strategies should be developed in order to stem the public health problems arising from the toxins. These include public education to create awareness on the health risks caused by mycotoxins, and enforcement of strict agricultural measures in handling the cereals to minimize contamination.

Abbreviations

AFB1 :

Aflatoxin B1

FB1 :

Fumonisin B1

HCC:

Hepatocellular carcinoma

HIV:

Human immunodeficiency virus

HPV:

Human papilloma virus

LMICs:

Low and middle-income countries

NCR:

Nairobi Cancer Registry

OAC:

Oesophageal adenocarcinoma

OC:

Oesophageal carcinoma

OSCC:

Oesophageal squamous cell carcinoma

SSA:

Sub-Saharan Africa

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.

    Article  CAS  PubMed  Google Scholar 

  2. Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet (London, England). 2013;381:400–12.

    Article  Google Scholar 

  3. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–52.

    Article  CAS  PubMed  Google Scholar 

  4. Bollschweiler E, Holscher AH, Metzger R. Histologic tumor type and the rate of complete response after neoadjuvant therapy for esophageal cancer. Future oncology (London, England). 2010;6:25–35.

    Article  CAS  Google Scholar 

  5. Liu S, Dai JY, Yao L, Li X, Reid B, Self S, Ma J, Chang Y, Feng S, Tapsoba Jde D, et al. Esophageal Adenocarcinoma and Its Rare Association with Barrett's Esophagus in Henan, China. PloS one. 2014;9:e110348.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Lindblad M, Ye W, Lindgren A, Lagergren J. Disparities in the classification of esophageal and cardia adenocarcinomas and their influence on reported incidence rates. Annals of surgery. 2006;243:479–85.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wang KK, Sampliner RE. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol. 2008;103:788–97.

    Article  PubMed  Google Scholar 

  8. Melhado RE, Alderson D, Tucker O. The changing face of esophageal cancer. Cancers. 2010;2:1379–404.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kamangar F, Chow WH, Abnet CC, Dawsey SM. Environmental causes of esophageal cancer. Gastroenterol Clin North Am. 2009;38:27–57. vii

    Article  PubMed  PubMed Central  Google Scholar 

  10. Yang CS, Chen X, Tu S. Etiology and Prevention of Esophageal Cancer. Gastrointestinal tumors. 2016;3:3–16.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Watanabe M. Risk factors and molecular mechanisms of esophageal cancer: differences between the histologic subtypes. J Cancer Metastasis Treat¦ Vol. 2015;1:1.

    Google Scholar 

  12. Kumagai N, Wakai T, Akazawa K, Ling Y, Wang S, Shan B, Okuhara Y, Hatakeyama Y, Kataoka H. Heavy alcohol intake is a risk factor for esophageal squamous cell carcinoma among middle-aged men: A case-control and simulation study. Mol Clin Oncol. 2013;1:811–6.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Morita M, Kumashiro R, Kubo N, Nakashima Y, Yoshida R, Yoshinaga K, Saeki H, Emi Y, Kakeji Y, Sakaguchi Y, et al. Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention. Int J Clin Oncol. 2010;15:126–34.

    Article  PubMed  Google Scholar 

  14. Zhang HZ, Jin GF, Shen HB. Epidemiologic differences in esophageal cancer between Asian and Western populations. Chin J Cancer. 2012;31:281–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Andrici J, Eslick GD. Hot Food and Beverage Consumption and the Risk of Esophageal Cancer: A Meta-Analysis. Am J Prev Med. 2015;49:952–60.

    Article  PubMed  Google Scholar 

  16. Castellsague X, Munoz N, De Stefani E, Victora CG, Castelletto R, Rolon PA: Influence of mate drinking, hot beverages and diet on esophageal cancer risk in South America. Int J Cancer 2000, 88:658-664.

  17. Islami F, Boffetta P, Ren JS, Pedoeim L, Khatib D, Kamangar F. High-temperature beverages and foods and esophageal cancer risk--a systematic review. Int J Cancer. 2009;125:491–524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen Y, Tong Y, Yang C, Gan Y, Sun H, Bi H, Cao S, Yin X, Lu Z. Consumption of hot beverages and foods and the risk of esophageal cancer: a meta-analysis of observational studies. BMC cancer. 2015;15:449.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Andrici J, Eslick GD. Mate consumption and the risk of esophageal squamous cell carcinoma: a meta-analysis. Dis Esophagus. 2013;26:807–16.

    Article  CAS  PubMed  Google Scholar 

  20. Lubin JH, De Stefani E, Abnet CC, Acosta G, Boffetta P, Victora C, Graubard BI, Munoz N, Deneo-Pellegrini H, Franceschi S, et al. Mate drinking and esophageal squamous cell carcinoma in South America: pooled results from two large multicenter case-control studies. Cancer Epidemiol Biomarkers Prev. 2014;23:107–16.

    Article  PubMed  Google Scholar 

  21. Ahsan H, Neugut AI. Radiation therapy for breast cancer and increased risk for esophageal carcinoma. Ann Intern Med. 1998;128:114–7.

    Article  CAS  PubMed  Google Scholar 

  22. Reid BJ, Li X, Galipeau PC, Vaughan TL. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010;10:87–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Engel LS, Chow WH, Vaughan TL, Gammon MD, Risch HA, Stanford JL, Schoenberg JB, Mayne ST, Dubrow R, Rotterdam H, et al. Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst. 2003;95:1404–13.

    Article  PubMed  Google Scholar 

  24. Vial M, Grande L, Pera M. Epidemiology of adenocarcinoma of the esophagus, gastric cardia, and upper gastric third. Recent results in cancer research Fortschritte der Krebsforschung Progres dans les recherches sur le cancer. 2010;182:1–17.

    PubMed  Google Scholar 

  25. Chen J, Zhang N, Ling Y, Wakai T, He Y, Wei L, Wang S, Akazawa K. Alcohol consumption as a risk factor for esophageal adenocarcinoma in North China. Tohoku J Exp Med. 2011;224:21–7.

    Article  PubMed  Google Scholar 

  26. Falk GW. Risk factors for esophageal cancer development. Surg Oncol Clin N Am. 2009;18:469–85.

    Article  PubMed  Google Scholar 

  27. Hardefeldt HA, Cox MR, Eslick GD. Association between human papillomavirus (HPV) and oesophageal squamous cell carcinoma: a meta-analysis. Epidemiol Community Health. 2014;142:1119–37.

    CAS  Google Scholar 

  28. Zhang SK, Guo LW, Chen Q, Zhang M, Liu SZ, Quan PL, Lu JB, Sun XB. Prevalence of human papillomavirus 16 in esophageal cancer among the Chinese population: a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2014;15:10143–9.

    Article  PubMed  Google Scholar 

  29. Zhang SK, Guo LW, Chen Q, Zhang M, Liu SZ, Quan PL, Lu JB, Sun XB. The association between human papillomavirus 16 and esophageal cancer in Chinese population: a meta-analysis. BMC cancer. 2015;15:1096.

    PubMed  Google Scholar 

  30. Xu W, Liu Z, Bao Q, Qian Z. Viruses, Other Pathogenic Microorganisms and Esophageal Cancer. Gastrointest Tumors. 2015;2:2–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Halec G, Schmitt M, Egger S, Abnet CC, Babb C, Dawsey SM, Flechtenmacher C, Gheit T, Hale M, Holzinger D, et al. Mucosal alpha-papillomaviruses are not associated with esophageal squamous cell carcinomas: Lack of mechanistic evidence from South Africa, China and Iran and from a world-wide meta-analysis. Int J Cancer. 2016;139:85–98.

    Article  CAS  PubMed  Google Scholar 

  32. Ludmir EB, Stephens SJ, Palta M, Willett CG, Czito BG. Human papillomavirus tumor infection in esophageal squamous cell carcinoma. J Gastrointest Oncol. 2015;6:287–95.

    PubMed  PubMed Central  Google Scholar 

  33. Koshiol J, Wei WQ, Kreimer AR, Chen W, Gravitt P, Ren JS, Abnet CC, Wang JB, Kamangar F, Lin DM, et al. No role for human papillomavirus in esophageal squamous cell carcinoma in China. Int J Cancer. 2010;127:93–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Von Knebel Doeberitz M. The causal role of human papillomavirus infections in non-anogenital cancers. It's time to ask for the functional evidence. Int J Cancer Suppl. 2016;139:9–11.

    Article  CAS  Google Scholar 

  35. Liu W, Snell JM, Jeck WR, Hoadley KA, Wilkerson MD, Parker JS, Patel N, Mlombe YB, Mulima G, Liomba NG, et al. Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis. JCI insight. 2016;1:e88755.

    PubMed  PubMed Central  Google Scholar 

  36. Pakzad R, Mohammadian-Hafshejani A, Khosravi B, Soltani S, Pakzad I, Mohammadian M, Salehiniya H, Momenimovahed Z. The incidence and mortality of esophageal cancer and their relationship to development in Asia. Ann Transl Med. 2016;4:29.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hendricks D, Parker MI. Oesophageal cancer in Africa. IUBMB life. 2002;53:263–8.

    Article  CAS  PubMed  Google Scholar 

  38. Arnold M, Soerjomataram I, Ferlay J, Forman D. Global incidence of oesophageal cancer by histological subtype in 2012. Gut. 2015;64:381–7.

    Article  PubMed  Google Scholar 

  39. Brown LM, Hoover R, Silverman D, Baris D, Hayes R, Swanson GM, Schoenberg J, Greenberg R, Liff J, Schwartz A, et al. Excess incidence of squamous cell esophageal cancer among US Black men: role of social class and other risk factors. Am J Emerg Med. 2001;153:114–22.

    CAS  Google Scholar 

  40. Prabhu A, Obi K, Lieberman D, Rubenstein JH. The Race-Specific Incidence of Esophageal Squamous Cell Carcinoma in Individuals With Exposure to Tobacco and Alcohol. Am J Gastroenterol. 2016;111:1718–25.

    Article  CAS  PubMed  Google Scholar 

  41. Cummings LC, Cooper GS. Descriptive epidemiology of esophageal carcinoma in the Ohio Cancer Registry. Cancer Cytopathol. 2008;32:87–92.

    Google Scholar 

  42. Sewram V, Sitas F, O'Connell D, Myers J. Tobacco and alcohol as risk factors for oesophageal cancer in a high incidence area in South Africa. Cancer Epidemiol. 2016;41:113–21.

    Article  PubMed  Google Scholar 

  43. Mwalwayo DS, Thole B. Prevalence of aflatoxin and fumonisins (B1 + B2) in maize consumed in rural Malawi. Toxicol Reports. 2016;3:173–9.

    Article  CAS  Google Scholar 

  44. Schaafsma T, Wakefield J, Hanisch R, Bray F, Schuz J, Joy EJ, Watts MJ, McCormack V. Africa’s Oesophageal Cancer Corridor: Geographic Variations in Incidence Correlate with Certain Micronutrient Deficiencies. PloS one. 2015;10:e0140107.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Chauhan NM, Washe AP, Minota T. Fungal infection and aflatoxin contamination in maize collected from Gedeo zone, Ethiopia. SpringerPlus. 2016;5:753.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Cheng ML, Zhang L, Borok M, Chokunonga E, Dzamamala C, Korir A, Wabinga HR, Hiatt RA, Parkin DM, Van Loon K: The incidence of oesophageal cancer in Eastern Africa: identification of a new geographic hot spot? Cancer epidemiology 2015, 39:143-149.

  47. Gakunga R, Parkin DM. Cancer registries in Africa 2014: A survey of operational features and uses in cancer control planning. Int J Cancer Suppl. 2015;137:2045–52.

    Article  CAS  Google Scholar 

  48. Eldoret Cancer Registry. http://afcrn.org/membership/members/101-eldoret. Accessed 29 Apr 2017.

  49. Korir A, Okerosi N, Ronoh V, Mutuma G, Parkin M. Incidence of cancer in Nairobi, Kenya (2004-2008). Int J Cancer. 2015;137:2053–9.

    Article  CAS  PubMed  Google Scholar 

  50. Korir A, Yu Wang E, Sasieni P, Okerosi N, Ronoh V, Maxwell Parkin D. Cancer risks in Nairobi (2000-2014) by ethnic group. Int J Cancer. 2017;140:788–97.

    Article  CAS  PubMed  Google Scholar 

  51. Ahmed N. Geographical incidence of oesophageal cancer in West Kenya. East Afr Med J. 1966;43:235–48.

    CAS  PubMed  Google Scholar 

  52. Ahmed N, Cook P. The incidence of cancer of the oesophagus in West Kenya. Br J Cancer. 1969;23:302–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. White RE, Abnet CC, Mungatana CK, Dawsey SM. Oesophageal cancer: a common malignancy in young people of Bomet District, Kenya. Lancet (London, England). 2002;360:462–3.

    Article  Google Scholar 

  54. 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. ISRN Oncol. 2013;2013:503249.

    PubMed  PubMed Central  Google Scholar 

  55. Tenge CN, Kuremu RT, Buziba NG, Patel K, Were PA. Burden and pattern of cancer in Western Kenya. East Afr Med J. 2009;86:7–10.

    Article  CAS  PubMed  Google Scholar 

  56. Dawsey SP, Tonui S, Parker RK, Fitzwater JW, Dawsey SM, White RE, Abnet CC. Esophageal cancer in young people: a case series of 109 cases and review of the literature. PloS one. 2010;5:e14080.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Parker RK, Dawsey SM, Abnet CC, White RE. Frequent occurrence of esophageal cancer in young people in western Kenya. Dis Esophagus. 2010;23:128–35.

    Article  CAS  PubMed  Google Scholar 

  58. Wakhisi J, Patel K, Buziba N, Rotich J. Esophageal cancer in north rift valley of western Kenya. Afr Health Sci. 2005;5:157–63.

    PubMed  PubMed Central  Google Scholar 

  59. Gatei DG, Odhiambo PA, Orinda DA, Muruka FJ, Wasunna A. Retrospective study of carcinoma of the esophagus in Kenya. Cancer Research. 1978;38:303–7.

    CAS  PubMed  Google Scholar 

  60. Mutiga SK, Hoffmann V, Harvey JW, Milgroom MG, Nelson RJ. Assessment of Aflatoxin and Fumonisin Contamination of Maize in Western Kenya. Phytopathology. 2015;105:1250–61.

    Article  CAS  PubMed  Google Scholar 

  61. Sirma AJ, Ouko EO, Murithi G, Mburugu C, Mapenay I, Ombui JN, Kang’ethe EK, Korhonen H. Prevalence of aflatoxin contamination in cereals from Nandi County, Kenya. Int J Agric Sci Vet Med. 2015;3:55–63.

    Google Scholar 

  62. Nieminen MT, Novak-Frazer L, Collins R, Dawsey SP, Dawsey SM, Abnet CC, White RE, Freedman ND, Mwachiro M, Bowyer P, et al. Alcohol and acetaldehyde in African fermented milk mursik – A possible etiological factor for high incidence of esophageal cancer in western Kenya. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2013;22:69–75.

    Article  CAS  Google Scholar 

  63. McCann JC. Maize and Grace : Africa's Encounter with a New World Crop, 1500-2000. Cambridge: Harvard University Press; 2009.

    Google Scholar 

  64. Wikipedia: Ugali. https://en.wikipedia.org/wiki/Ugali. Accessed 13 Mar 2017.

  65. Kipkorir BE. People of the Rift Valley : [Kalenjin]. London: Evans; 1978.

    Google Scholar 

  66. Papas RK, Sidle JE, Wamalwa ES, Okumu TO, Bryant KL, Goulet JL, Maisto SA, Braithwaite RS, Justice AC. Estimating Alcohol Content of Traditional Brew in Western Kenya Using Culturally Relevant Methods: The Case for Cost Over Volume. AIDS and behavior. 2010;14:836–44.

    Article  PubMed  Google Scholar 

  67. Lo TQ, Oeltmann JE, Odhiambo FO, Beynon C, Pevzner E, Cain KP, Laserson KF, Phillips-Howard PA. Alcohol use, drunkenness and tobacco smoking in rural western Kenya. Tropical medicine & international health : TM & IH. 2013;18:506–15.

    Article  CAS  Google Scholar 

  68. Darwish WS, Ikenaka Y, Nakayama SM, Ishizuka M. An overview on mycotoxin contamination of foods in Africa. The Journal of veterinary medical science. 2014;76:789–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Chilaka CA, De Boevre M, Atanda OO, De Saeger S: The Status of Fusarium Mycotoxins in Sub-Saharan Africa: A Review of Emerging Trends and Post-Harvest Mitigation Strategies towards Food Control. Toxins 2017, 9:19.

  70. Zain ME. Impact of mycotoxins on humans and animals. J Saudi Chemical Soc. 2011;15:129–44.

    Article  CAS  Google Scholar 

  71. Nesic K, Ivanovic S, Nesic V. Fusarial toxins: secondary metabolites of Fusarium fungi. Rev Environ Contam Toxicol. 2014;228:101–20.

    CAS  PubMed  Google Scholar 

  72. Marin S, Ramos AJ, Cano-Sancho G, Sanchis V. Mycotoxins: Occurrence, toxicology, and exposure assessment. Food Chem Toxicol. 2013;60:218–37.

    Article  CAS  PubMed  Google Scholar 

  73. Meredith FI. Isolation and characterization of fumonisins. Methods Enzymol. 2000;311:361–73.

    Article  CAS  PubMed  Google Scholar 

  74. Yazar S, Omurtag GZ. Fumonisins, trichothecenes and zearalenone in cereals. Int J Mol Sci. 2008;9:2062–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mwanda OW, Otieno CF, Omonge E. Acute aflatoxicosis: case report. East Afr Med J. 2005;82:320–4.

    CAS  PubMed  Google Scholar 

  76. Pitt JI. Toxigenic fungi and mycotoxins. Br Med Bull. 2000;56:184–92.

    Article  CAS  PubMed  Google Scholar 

  77. Shuaib FM, Ehiri J, Abdullahi A, Williams JH, Jolly PE. Reproductive health effects of aflatoxins: a review of the literature. Reprod Toxicol (Elmsford, NY). 2010;29:262–70.

    Article  CAS  Google Scholar 

  78. Stockmann-Juvala H, Savolainen K. A review of the toxic effects and mechanisms of action of fumonisin B1. Hum Exp Toxicol. 2008;27:799–809.

    Article  CAS  PubMed  Google Scholar 

  79. Ribeiro DH, Ferreira FL, da Silva VN, Aquino S, Correa B: Effects of aflatoxin B(1) and fumonisin B(1) on the viability and induction of apoptosis in rat primary hepatocytes. Int J Mol Sci 2010, 11:1944-1955.

  80. Williams JH, Grubb JA, Davis JW, Wang JS, Jolly PE, Ankrah NA, Ellis WO, Afriyie-Gyawu E, Johnson NM, Robinson AG, Phillips TD. HIV and hepatocellular and esophageal carcinomas related to consumption of mycotoxin-prone foods in sub-Saharan Africa. Am J Clin Nutr. 2010;92:154–60.

    Article  CAS  PubMed  Google Scholar 

  81. Wu F, Groopman JD, Pestka JJ. Public health impacts of foodborne mycotoxins. Ann Rev Food Sci Technol. 2014;5:351–72.

    Article  CAS  Google Scholar 

  82. Voss KA, Riley RT, Norred WP, Bacon CW, Meredith FI, Howard PC, Plattner RD, Collins TF, Hansen DK, Porter JK. An overview of rodent toxicities: liver and kidney effects of fumonisins and Fusarium moniliforme. Environ Health Perspect. 2001;109:259–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Gelderblom WC, Abel S, Smuts CM, Marnewick J, Marasas WF, Lemmer ER, Ramljak D. Fumonisin-induced hepatocarcinogenesis: mechanisms related to cancer initiation and promotion. Environ Health Perspect. 2001;109(Suppl 2):291–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Bidlack WR, Cohen SM, Goldsworthy TL, Hard GC, Howard PC, Riley RT, Voss KA. Implications of apoptosis for toxicity, carcinogenicity, and risk assessment: fumonisin B(1) as an example. Toxicol Sci. 2001;61:6–17.

    Article  PubMed  Google Scholar 

  85. Wild CP, Gong YY. Mycotoxins and human disease: a largely ignored global health issue. Carcinogenesis. 2010;31:71–82.

    Article  CAS  PubMed  Google Scholar 

  86. Norred WP. Fumonisins--mycotoxins produced by Fusarium moniliforme. J Toxicol Environ Health. 1993;38:309–28.

    Article  CAS  PubMed  Google Scholar 

  87. Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nagao M. Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin. Biochem Biophys Res Commun. 1996;220:160–5.

    Article  CAS  PubMed  Google Scholar 

  88. Ramljak D, Calvert RJ, Wiesenfeld PW, Diwan BA, Catipovic B, Marasas WF, Victor TC, Anderson LM, Gelderblom WC. A potential mechanism for fumonisin B(1)-mediated hepatocarcinogenesis: cyclin D1 stabilization associated with activation of Akt and inhibition of GSK-3beta activity. Carcinogenesis. 2000;21:1537–46.

    CAS  PubMed  Google Scholar 

  89. Gelderblom WC, Kriek NP, Marasas WF, Thiel PG. Toxicity and carcinogenicity of the Fusarium moniliforme metabolite, fumonisin B1, in rats. Carcinogenesis. 1991;12:1247–51.

    Article  CAS  PubMed  Google Scholar 

  90. Dragan YP, Bidlack WR, Cohen SM, Goldsworthy TL, Hard GC, Howard PC, Riley RT, Voss KA. Implications of apoptosis for toxicity, carcinogenicity, and risk assessment: fumonisin B(1) as an example. Toxicol Sci. 2001;61:6–17.

    Article  CAS  PubMed  Google Scholar 

  91. Keck BB, Bodine AB. The effects of fumonisin B1 on viability and mitogenic response of avian immune cells. Poultry Sci. 2006;85:1020–4.

    Article  CAS  Google Scholar 

  92. Soriano JM, Gonzalez L, Catala AI. Mechanism of action of sphingolipids and their metabolites in the toxicity of fumonisin B1. Prog Lipid Res. 2005;44:345–56.

    Article  CAS  PubMed  Google Scholar 

  93. Ciacci-Zanella JR, Merrill AH Jr, Wang E, Jones C. Characterization of cell-cycle arrest by fumonisin B1 in CV-1 cells. Food Chem Toxicol. 1998;36:791–804.

    Article  CAS  PubMed  Google Scholar 

  94. Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM, Aggarwal D. Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr. 2004;80:1106–22.

    CAS  PubMed  Google Scholar 

  95. Shephard GS. Impact of mycotoxins on human health in developing countries. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2008;25:146–51.

    Article  CAS  PubMed  Google Scholar 

  96. Kew MC. Interaction Between Aflatoxin B1 and Other Risk Factors in Hepatocarcinogenesis. In: Mycotoxins in Food, Feed and Bioweapons. Edited by Rai M, Varma A. Berlin: Springer Berlin Heidelberg; 2010. p. 93–111.

  97. Liu Y, Wu F. Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. Environ Health Perspect. 2010;118:818–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Magnussen A, Parsi MA. Aflatoxins, hepatocellular carcinoma and public health. World J Gastroenterol. 2013;19:1508–12.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Hamid AS, Tesfamariam IG, Zhang Y, Zhang ZG. Aflatoxin B1-induced hepatocellular carcinoma in developing countries: Geographical distribution, mechanism of action and prevention. Oncol Letters. 2013;5:1087–92.

    CAS  Google Scholar 

  100. Kucukcakan B, Hayrulai-Musliu Z. Challenging Role of Dietary Aflatoxin B1 Exposure and Hepatitis B Infection on Risk of Hepatocellular Carcinoma. Open Access Macedonian J Med Sci. 2015;3:363–9.

    Article  Google Scholar 

  101. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International journal of cancer. 2010;127:2893–917.

    Article  CAS  PubMed  Google Scholar 

  102. Wu HC, Santella R. The Role of Aflatoxins in Hepatocellular Carcinoma. Hepatitis Monthly. 2012;12:e7238.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Gnonlonfin GJ, Hell K, Adjovi Y, Fandohan P, Koudande DO, Mensah GA, Sanni A, Brimer L. A review on aflatoxin contamination and its implications in the developing world: a sub-Saharan African perspective. Crit Rev Food Sci Nutr. 2013;53:349–65.

    Article  CAS  PubMed  Google Scholar 

  104. Kew MC. Aflatoxins as a cause of hepatocellular carcinoma. J Gastrointestin Liver Dis. 2013;22:305–10.

    PubMed  Google Scholar 

  105. Park US, Su JJ, Ban KC, Qin L, Lee EH, Lee YI. Mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis B virus infection and intake of aflatoxin B1. Gene. 2000;251:73–80.

    Article  CAS  PubMed  Google Scholar 

  106. Su JJ, Li Y, Ban KC, Qin LL, Wang HY, Yang C, Ou C, Duan XX, Li YY, Yan RQ. Alteration of p53 gene during tree shrews' hepatocarcinogenesis. Zhonghua Gan Zang Bing Za Zhi. 2003;11:159–61.

    CAS  PubMed  Google Scholar 

  107. Xue KX. Molecular genetic and epigenetic mechanisms of hepatocarcinogenesis. Ai zheng. 2005;24:757–68.

    CAS  PubMed  Google Scholar 

  108. Shirabe K, Toshima T, Taketomi A, Taguchi K, Yoshizumi T, Uchiyama H, Harimoto N, Kajiyama K, Egashira A, Maehara Y. Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan. Liver Int. 2011;31:1366–72.

    Article  CAS  PubMed  Google Scholar 

  109. Ghasemi-Kebria F, Joshaghani H, Taheri NS, Semnani S, Aarabi M, Salamat F, Roshandel G. Aflatoxin contamination of wheat flour and the risk of esophageal cancer in a high risk area in Iran. Cancer Epidemiol. 2013;37:290–3.

    Article  CAS  PubMed  Google Scholar 

  110. Ajanga S, Hillocks RJ. Maize cob rot in Kenya and its association with stalk borer damage. Crop Protection. 2000;19:297–300.

    Article  Google Scholar 

  111. Alakonya AE, Monda EO, Ajanga S. FUMONISIN B₁ AND AFLATOXIN B₁ LEVELS IN KENYAN MAIZE. J Plant Pathol. 2009;91:459–64.

    CAS  Google Scholar 

  112. Alakonya AE, Monda EO, Ajanga S. Effect of delayed harvesting on maize ear rot in Western Kenya. Am Eurasian J Agric Environ Sci. 2008;4:372–380.

  113. Logrieco A, Moretti A, Perrone G, Mulè G. Biodiversity of complexes of mycotoxigenic fungal species associated with Fusarium ear rot of maize and Aspergillus rot of grape. Int J Food Microbiol. 2007;119:11–6.

    Article  CAS  PubMed  Google Scholar 

  114. Mutiga SK, Were V, Hoffmann V, Harvey JW, Milgroom MG, Nelson RJ. Extent and drivers of mycotoxin contamination: inferences from a survey of kenyan maize mills. Phytopathol. 2014;104:1221–31.

    Article  CAS  Google Scholar 

  115. Probst C, Schulthess F, Cotty PJ. Impact of Aspergillus section Flavi community structure on the development of lethal levels of aflatoxins in Kenyan maize (Zea mays). J Appl Microbiol. 2010;108:600–10.

    Article  CAS  PubMed  Google Scholar 

  116. Nyaga P: Kenya: Report on Aflatoxin Contamination in Maize: Error! Hyperlink reference not valid. PRESENTATION(AFLATOXIN)%20JUNE%202010.pdf. Accessed on 13/03/2017. In Book Kenya: Report on Aflatoxin Contamination in Maize: Error! Hyperlink reference not valid. PRESENTATION(AFLATOXIN)%20JUNE%202010.pdf Accessed on 13/03/2017 (Editor ed.^eds.). City; 2010.

  117. Muthomi JW, Ndung’u JK, Gathumbi JK, Mutitu EW, Wagacha JM. The occurrence of Fusarium species and mycotoxins in Kenyan wheat. Crop Protection. 2008;27:1215–9.

    Article  CAS  Google Scholar 

  118. Lewis L, Onsongo M, Njapau H, Schurz-Rogers H, Luber G, Kieszak S, Nyamongo J, Backer L, Dahiye AM, Misore A, et al. Aflatoxin contamination of commercial maize products during an outbreak of acute aflatoxicosis in eastern and central Kenya. Environ Health Perspect. 2005;113:1763–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Probst C, Njapau H, Cotty PJ. Outbreak of an acute aflatoxicosis in Kenya in 2004: identification of the causal agent. Appl Environ Microbiol. 2007;73:2762–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Barrett JR. Liver Cancer and Aflatoxin: New Information from the Kenyan Outbreak. Environ Health Perspect. 2005;113:A837–8.

    Article  PubMed Central  Google Scholar 

  121. Mutegi CK, Ngugi HK, Hendriks SL, Jones RB. Prevalence and factors associated with aflatoxin contamination of peanuts from Western Kenya. Int J Food Microbiol. 2009;130:27–34.

    Article  CAS  PubMed  Google Scholar 

  122. Kang'ethe E. Situation analysis: Improving food safety in the maize value chain in Kenya. A Report Prepared for FAO by Prof. Erastus Kang'ethe, College of Agriculture and Veterinary, Science University of Nairobi (September 2011). Available on http://www.fao.org/fileadmin/user_upload/agns/pdf/WORKING_PAPER_AFLATOXIN_REPORTDJ10thOctober.pdf. Accessed 30 Oct 2017.

  123. Kang’ethe EK, Lang’a KA. Aflatoxin B1 and M1 contamination of animal feeds and milk from urban centers in Kenya. Afr Health Sci. 2009;9:218–26.

    PubMed  PubMed Central  Google Scholar 

  124. Kirui MC, Alakonya AE, Talam KK, Tohru G, Bii CC. Total aflatoxin, fumonisin and deoxynivalenol contamination of busaa in Bomet county, Kenya. African J Biotechnol. 2014;13.

  125. Ariga J, Jayne TS, Nyoro JK: Factors driving the growth in fertilizer consumption in Kenya, 1990-2005 : sustaining the momentum in Kenya and lessons for broader replicability in sub-Saharan Africa. Nairobi, Kenya: Tegemeo Institute of Agricultural Policy and Development; 2008.

    Google Scholar 

  126. Kirimi L. History of Kenyan maize production, marketing and policies. Kenya: Tegemeo Institute of Agricultural Policy and Development Nairobi; 2012.

    Google Scholar 

  127. Yoshida M. The historical background to maize marketing in Kenya and its implications for future marketing reorganisation; 1966. Available on: https://opendocs.ids.ac.uk/opendocs/bitstream/handle/123456789/1502/EDRP91-329711.pdf?sequence=1. Accessed 30 Oct 2017.

  128. CMD SOURCEWATCH. The Center for Media and Democracy: The Adoption of Maize in Kenya. http://www.sourcewatch.org/index.php/The_Adoption_of_Maize_in_Kenya. Accessed 16 Mar 2017.

  129. Overton JD. Social Control and Social Engineering: African Reserves in Kenya 1895–1920. Environment and Planning D: Society and Space. 1990;8:163–74.

    Article  Google Scholar 

  130. Parsons T. Local Responses to the Ethnic Geography of Colonialism in the Gusii Highlands of British-Ruled Kenya. Ethnohistory. 2011;58:491–523.

    Article  Google Scholar 

  131. Wikipedia: Kalenjin people. https://en.wikipedia.org/wiki/Kalenjin_people. Accessed 25 Jan 2017.

  132. Miracle MP. The introduction and spread of maize in Africa. Journal of African History. 1965:39–55.

  133. Trapman C. Change in administrative structures: a case study of Kenyan agricultural development / Christopher Trapman. London: Overseas Development Institute; 1974. Available on: https://nla.gov.au/nla.cat-vn2636261. Accessed 30 Oct 2017.

  134. Collier W. Colonial maize and climate: limits of agricultural development for adaptation in Rift Valley, Kenya. Tropical Resources: Bulletin of the Yale Tropical Resources Institute. 2010;29:10–5.

    Google Scholar 

  135. Jayne T, Smale M. Maize in Eastern and Southern Africa: Seeds of Success in Retrospect. In Book Maize in Eastern and Southern Africa: Seeds of Success in Retrospect (Editor ed.^eds.). City; 2005.

  136. Standardmedia. Farmers advised against drying maize in the open: Standardmedia: Farmers advised against drying maize in the open: https://www.standardmedia.co.ke/article/2000102518/farmers-advised-against-drying-maize-in-the-open. Accessed 1 May 2017.

  137. Hoffmann V, Mutiga S, Harvey J, Nelson R, Milgroom M: Aflatoxin contamination of maize in Kenya: Observability and mitigation behavior. In Book Aflatoxin contamination of maize in Kenya: Observability and mitigation behavior (Editor ed.^eds.). City; 2013.

  138. Kang’ethe EK, M'Ibui GM, Randolph TF, Lang’at AK. Prevalence of aflatoxin M1 and B1 in milk and animal feeds from urban smallholder dairy production in Dagoretti Division, Nairobi, Kenya. East Afr Med J. 2007;84:S83–6.

    PubMed  Google Scholar 

  139. Hoffmann V, Mutiga S, Harvey J, Milgroom M, Nelson R: A Market for lemons: Maize in Kenya. 2012.

    Google Scholar 

  140. Leroy JL, Wang JS, Jones K. Serum aflatoxin B(1)-lysine adduct level in adult women from Eastern Province in Kenya depends on household socio-economic status: A cross sectional study. Social Sci Med (1982). 2015;146:104–10.

    Article  Google Scholar 

  141. Yard EE, Daniel JH, Lewis LS, Rybak ME, Paliakov EM, Kim AA, Montgomery JM, Bunnell R, Abudo MU, Akhwale W, et al. Human aflatoxin exposure in Kenya, 2007: a cross-sectional study. Food additives & contaminants Part A, Chemistry, analysis, control, exposure & risk assessment. 2013;30:1322–31.

    Article  CAS  Google Scholar 

  142. Mbugua SK, Gathumbi J. The contamination of Kenyan lager beers with Fusarium mycotoxins. J Inst Brewing. 2004;110:227–9.

    Article  CAS  Google Scholar 

  143. Vaughan TL, Davis S, Kristal A, Thomas DB. Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 1995;4:85–92.

    CAS  PubMed  Google Scholar 

  144. Gammon MD, Schoenberg JB, Ahsan H, Risch HA, Vaughan TL, Chow WH, Rotterdam H, West AB, Dubrow R, Stanford JL, et al. Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst. 1997;89:1277–84.

    Article  CAS  PubMed  Google Scholar 

  145. De Stefani E, Barrios E, Fierro L. Black (air-cured) and blond (flue-cured) tobacco and cancer risk. III: Oesophageal cancer. Eur J Cancer. 1993;29a:763–6.

    Article  CAS  PubMed  Google Scholar 

  146. Lee CH, Wu DC, Lee JM, Wu IC, Goan YG, Kao EL, Huang HL, Chan TF, Chou SH, Chou YP, et al. Carcinogenetic impact of alcohol intake on squamous cell carcinoma risk of the oesophagus in relation to tobacco smoking. Eur J Cancer. 2007;43:1188–99.

    Article  CAS  PubMed  Google Scholar 

  147. Lopes CF, de Angelis BB, Prudente HM, de Souza BV, Cardoso SV, de Azambuja Ribeiro RI. Concomitant consumption of marijuana, alcohol and tobacco in oral squamous cell carcinoma development and progression: recent advances and challenges. Arch Oral Biol 2012, 57:1026-1033.

  148. Prabhu A, Obi KO, Rubenstein JH. The synergistic effects of alcohol and tobacco consumption on the risk of esophageal squamous cell carcinoma: a meta-analysis. Am J Gastroenterol. 2014;109:822–7.

    Article  PubMed  Google Scholar 

  149. Peng Q, Chen H, Huo JR. Alcohol consumption and corresponding factors: A novel perspective on the risk factors of esophageal cancer. Oncology Letters. 2016;11:3231–9.

    PubMed  PubMed Central  Google Scholar 

  150. Toh Y, Oki E, Ohgaki K, Sakamoto Y, Ito S, Egashira A, Saeki H, Kakeji Y, Morita M, Sakaguchi Y, et al. Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: molecular mechanisms of carcinogenesis. Int J Clin Oncol. 2010;15:135–44.

    Article  CAS  PubMed  Google Scholar 

  151. Wang Y, Ji R, Wei X, Gu L, Chen L, Rong Y, Wang R, Zhang Z, Liu B, Xia S. Esophageal squamous cell carcinoma and ALDH2 and ADH1B polymorphisms in Chinese females. Asian Pac J Cancer Prev. 2011;12:2065–8.

    PubMed  Google Scholar 

  152. Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A. The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption. PLoS Med. 2009;6

  153. Yang SJ, Wang HY, Li XQ, Du HZ, Zheng CJ, Chen HG, Mu XY, Yang CX. Genetic polymorphisms of ADH2 and ALDH2 association with esophageal cancer risk in southwest China. World J Gastroenterol. 2007;13:5760–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Wu CF, Wu DC, Hsu HK, Kao EL, Lee JM, Lin CC, Wu MT. Relationship between genetic polymorphisms of alcohol and aldehyde dehydrogenases and esophageal squamous cell carcinoma risk in males. World J Gastroenterol. 2005;11:5103–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Yokoyama A, Mizukami T, Yokoyama T. Genetic polymorphisms of alcohol dehydrogense-1B and aldehyde dehydrogenase-2, alcohol flushing, mean corpuscular volume, and aerodigestive tract neoplasia in Japanese drinkers. Adv Exp Med Biol. 2015;815:265–79.

    Article  CAS  PubMed  Google Scholar 

  156. Ding JH, Li SP, Cao HX, Wu JZ, Gao CM, Liu YT, Zhou JN, Chang J, Yao GH. Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for esophageal cancer in a Chinese population. J Hum Genet. 2010;55:97–102.

    Article  CAS  PubMed  Google Scholar 

  157. Zhang GH, Mai RQ, Huang B. Meta-analysis of ADH1B and ALDH2 polymorphisms and esophageal cancer risk in China. World J Gastroenterol. 2010;16:6020–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M. Recent Advances From Basic and Clinical Studies of Esophageal Squamous Cell Carcinoma. Gastroenterol. 2015;149:1700–15.

    Article  Google Scholar 

  159. Yokoyama A, Omori T, Yokoyama T. Alcohol and aldehyde dehydrogenase polymorphisms and a new strategy for prevention and screening for cancer in the upper aerodigestive tract in East Asians. Keio J Med. 2010;59:115–30.

    Article  PubMed  Google Scholar 

  160. Cui R, Kamatani Y, Takahashi A, Usami M, Hosono N, Kawaguchi T, Tsunoda T, Kamatani N, Kubo M, Nakamura Y, Matsuda K. Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. Gastroenterol. 2009;137:1768–75.

    Article  CAS  Google Scholar 

  161. Xue J, Yang S, Seng S. Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN. Cancers. 2014;6:1138–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Arredondo J, Chernyavsky AI, Grando SA. Nicotinic receptors mediate tumorigenic action of tobacco-derived nitrosamines on immortalized oral epithelial cells. Cancer Biol Ther. 2006;5:511–7.

    Article  CAS  PubMed  Google Scholar 

  163. Hecht SS, Stepanov I, Carmella SG. Exposure and Metabolic Activation Biomarkers of Carcinogenic Tobacco-Specific Nitrosamines. Acc Chem Res. 2016;49:106–14.

    Article  CAS  PubMed  Google Scholar 

  164. Stepanov I, Sebero E, Wang R, Gao YT, Hecht SS, Yuan JM. Tobacco-specific N-nitrosamine exposures and cancer risk in the Shanghai Cohort Study: remarkable coherence with rat tumor sites. Int J Cancer. 2014;134:2278–83.

    Article  CAS  PubMed  Google Scholar 

  165. Colón-Singh R. Mursik, Kenya's Secret Superfood: Kenyan athletes are famous for winning marathons and competitions around the world. Could their secret be a little-known super food known as 'mursik'? https://www.finedininglovers.com/stories/ash-yogurt-mursik-kenya-super-food. Accessed 15 May 2016.

  166. Bett C. Indigenous milk preservation technology among the Kalenjin of Kenya. http://www.agriculturesnetwork.org/magazines/east-africa/63-regional-food-systems/indigenous-milk-preservation-kalenjin, by Charles Kipsang Bett. Accessed 25 Jan 2016.

  167. Davoodi H, Esmaeili S, Mortazavian A. Effects of milk and milk products consumption on cancer: a review. Comprehensive Reviews Food Sci Food Safety. 2013;12:249–64.

    Article  CAS  Google Scholar 

  168. Abedin-Do A, Taherian-Esfahani Z, Ghafouri-Fard S, Ghafouri-Fard S, Motevaseli E. Immunomodulatory effects of Lactobacillus strains: emphasis on their effects on cancer cells. Immunother. 2015;7:1307–29.

    Article  CAS  Google Scholar 

  169. Chen HY, Mollstedt O, Tsai MH, Kreider RB. Potential clinical applications of multi-functional milk proteins and peptides in cancer management. Current medicinal chemistry. 2014;21:2424–37.

    Article  CAS  PubMed  Google Scholar 

  170. S-b T, Yu J-c, W-m K, Ma Z-q, Ye X, Z-j C. Association between Dairy Intake and Gastric Cancer: A Meta-Analysis of Observational Studies. PloS one. 2014;9:e101728.

    Article  CAS  Google Scholar 

  171. Nair MRB, Chouhan D, Sen Gupta S, Chattopadhyay S. Fermented Foods: Are They Tasty Medicines for Helicobacter pylori Associated Peptic Ulcer and Gastric Cancer? Frontiers Microbiol. 2016;7:1148.

    Article  Google Scholar 

  172. Stepien M, Chajes V, Romieu I. The role of diet in cancer: the epidemiologic link. Salud publica de Mexico. 2016;58:261–73.

    Article  PubMed  Google Scholar 

  173. Uebelacker M, Lachenmeier DW. Quantitative determination of acetaldehyde in foods using automated digestion with simulated gastric fluid followed by headspace gas chromatography. J Automated Methods Manage Chem. 2011;2011:907317.

    Article  Google Scholar 

  174. Nduko JM, Matofari JW, Nandi ZO, Sichangi MB. Spontaneously fermented kenyan milk products: A review of the current state and future perspectives. Afr J Food Sci. 2017;11:1–11.

    Article  Google Scholar 

  175. Muigei SC, Shitandi A, Muliro P, Bitonga OR. Production of exopolysaccharides in the Kenyan fermented milk, Mursik. Int J Sci Res. 2013;2:79–89.

  176. Inoue T, Nagatomi Y, Uyama A, Mochizuki N. Degradation of aflatoxin B1 during the fermentation of alcoholic beverages. Toxins. 2013;5:1219–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Chen M, Chang CH, Tao L, Lu C. Residential Exposure to Pesticide During Childhood and Childhood Cancers: A Meta-Analysis. Pediatrics. 2015;136:719–29.

    Article  PubMed  Google Scholar 

  178. Turner MC, Wigle DT, Krewski D. Residential pesticides and childhood leukemia: a systematic review and meta-analysis. Ciencia Saude Coletiva. 2011;16:1915–31.

    Article  PubMed  Google Scholar 

  179. Carolyn Sanford D, David Sabapathy M, Heather Morrison M, Katherine Gaudreau R. Pesticides and Human Health – PrinceEdward Island Canada. https://www.princeedwardisland.ca/sites/.../publications/cpho_pesticide_part_1.pdf. Accessed 02 Apr 2016.

  180. Delancey JO, Alavanja MC, Coble J, Blair A, Hoppin JA, Austin HD, Beane Freeman LE. Occupational exposure to metribuzin and the incidence of cancer in the Agricultural Health Study. Ann Epidemiol. 2009;19:388–95.

    Article  PubMed  PubMed Central  Google Scholar 

  181. Myers JP, Antoniou MN, Blumberg B, Carroll L, Colborn T, Everett LG, Hansen M, Landrigan PJ, Lanphear BP, Mesnage R, et al. Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. Environ Health. 2016;15:19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Weichenthal S, Moase C, Chan P. A review of pesticide exposure and cancer incidence in the agricultural health study cohort. Ciencia Saude Coletiva. 2012;17:255–70.

    Article  PubMed  Google Scholar 

  183. Park SK, Kang D, Beane-Freeman L, Blair A, Hoppin JA, Sandler DP, Lynch CF, Knott C, Gwak J, Alavanja M. Cancer incidence among paraquat exposed applicators in the agricultural health study: prospective cohort study. Int J Occup Environ Health. 2009;15:274–81.

    Article  PubMed  PubMed Central  Google Scholar 

  184. Clapp RW, Jacobs MM, Loechler EL. Environmental and occupational causes of cancer: new evidence 2005-2007. Rev Environ Health. 2008;23:1–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Lynch SM, Rusiecki JA, Blair A, Dosemeci M, Lubin J, Sandler D, Hoppin JA, Lynch CF, Alavanja MC. Cancer incidence among pesticide applicators exposed to cyanazine in the agricultural health study. Environ Health Perspect. 2006;114:1248–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Rusiecki JA, Hou L, Lee WJ, Blair A, Dosemeci M, Lubin JH, Bonner M, Samanic C, Hoppin JA, Sandler DP, Alavanja MC. Cancer incidence among pesticide applicators exposed to metolachlor in the Agricultural Health Study. Int J Cancer. 2006;118:3118–23.

    Article  CAS  PubMed  Google Scholar 

  187. Jansson C, Plato N, Johansson AL, Nyren O, Lagergren J. Airborne occupational exposures and risk of oesophageal and cardia adenocarcinoma. Occup Environ Med. 2006;63:107–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Yildirim M, Kaya V, Yildiz M, Demirpence O, Gunduz S, Dilli UD. Esophageal cancer, gastric cancer and the use of pesticides in the southwestern of Turkey. Asian Pac J Cancer Prev. 2014;15:2821–3.

    Article  PubMed  Google Scholar 

  189. Lee WJ, Lijinsky W, Heineman EF, Markin RS, Weisenburger DD, Ward MH. Agricultural pesticide use and adenocarcinomas of the stomach and oesophagus. Occup Environ Med. 2004;61:743–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Chrisman Jde R, Koifman S, de Novaes Sarcinelli P, Moreira JC, Koifman RJ, Meyer A: Pesticide sales and adult male cancer mortality in Brazil. Int J Hyg Environ Health 2009, 212:310-321.

  191. Taghavi N, Biramijamal F, Abbaszadegan MR, Khademi H, Sotoudeh M, Khoshbakht S. P21(waf1/cip1) gene polymorphisms and possible interaction with cigarette smoking in esophageal squamous cell carcinoma in northeastern Iran: a preliminary study. Arch Iran Med. 2010;13:235–42.

    CAS  PubMed  Google Scholar 

  192. Yao W, Qin X, Qi B, Lu J, Guo L, Liu F, Liu S, Zhao B. Association of p53 expression with prognosis in patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7:7158–63.

    PubMed  PubMed Central  Google Scholar 

  193. Hong L, Han Y, Zhang H, Fan D. Prognostic markers in esophageal cancer: from basic research to clinical use. Expert Rev Gastroenterol Hepatol. 2015;9:887–9.

    Article  CAS  PubMed  Google Scholar 

  194. Ide S, Toiyama Y, Shimura T, Kawamura M, Yasuda H, Saigusa S, Ohi M, Tanaka K, Mohri Y, Kusunoki M. Angiopoietin-Like Protein 2 Acts as a Novel Biomarker for Diagnosis and Prognosis in Patients with Esophageal Cancer. Ann Surg Oncol. 2015;22:2585–92.

    Article  PubMed  Google Scholar 

  195. Lao-Sirieix P, Caldas C, Fitzgerald RC. Genetic predisposition to gastro-oesophageal cancer. Curr Opin Genet Dev. 2010;20:210–7.

    Article  CAS  PubMed  Google Scholar 

  196. Li D, Dandara C, Parker MI. Association of cytochrome P450 2E1 genetic polymorphisms with squamous cell carcinoma of the oesophagus. Clin Chem Lab Med. 2005;43:370–5.

    CAS  PubMed  Google Scholar 

  197. Guo YM, Wang Q, Liu YZ, Chen HM, Qi Z, Guo QH. Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males. World J Gastroenterol. 2008;14:1444–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Bergheim I, Wolfgarten E, Bollschweiler E, Holscher AH, Bode C, Parlesak A. Cytochrome P450 levels are altered in patients with esophageal squamous-cell carcinoma. World J Gastroenterol. 2007;13:997–1002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Poljak M, Kocjan BJ, Hošnjak L. Role of human papillomaviruses in esophageal carcinoma: an updated systematic review from 1982 to 2013. Future Virology. 2014;9:69–86.

    Article  CAS  Google Scholar 

  200. Kunzmann AT, Graham S, McShane CM, Doyle J, Tommasino M, Johnston B, Jamison J, James JA, McManus D, Anderson LA. The prevalence of viral agents in esophageal adenocarcinoma and Barrett's esophagus: a systematic review. Eur J Gastroenterol Hepatol. 2017;29:817–25.

    Article  CAS  PubMed  Google Scholar 

  201. Wilkerson MD, Parker JS, Patel N, Mlombe YB, Mulima G, Liomba NG, Wolf LL, Shores CG, Gopal S, Sharpless NE, et al. Human papillomavirus-related esophageal cancer survival: A systematic review and meta-analysis. JCI insight. 2016;95:e5318.

    Google Scholar 

  202. Turkay DO, Vural C, Sayan M, Gurbuz Y. Detection of human papillomavirus in esophageal and gastroesophageal junction tumors: A retrospective study by real-time polymerase chain reaction in an instutional experience from Turkey and review of literature. Pathol Res Pract. 2016;212:77–82.

    Article  CAS  PubMed  Google Scholar 

  203. Petrick JL, Wyss AB, Butler AM, Cummings C, Sun X, Poole C, Smith JS, Olshan AF. Prevalence of human papillomavirus among oesophageal squamous cell carcinoma cases: systematic review and meta-analysis. Br J Cancer. 2014;110:2369–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Dabrowski A, Kwasniewski W, Skoczylas T, Bednarek W, Kuzma D, Gozdzicka-Jozefiak A. Incidence of human papilloma virus in esophageal squamous cell carcinoma in patients from the Lublin region. World J Gastroenterol. 2012;18:5739–44.

    Article  PubMed  PubMed Central  Google Scholar 

  205. Cao F, Han H, Zhang F, Wang B, Ma W, Wang Y, Sun G, Shi M, Ren Y, Cheng Y. HPV infection in esophageal squamous cell carcinoma and its relationship to the prognosis of patients in northern China. TheScientificWorldJournal. 2014;2014:804738.

    PubMed  PubMed Central  Google Scholar 

  206. Wang J, Zhao L, Yan H, Che J, Huihui L, Jun W, Liu B, Cao B. A Meta-Analysis and Systematic Review on the Association between Human Papillomavirus (Types 16 and 18) Infection and Esophageal Cancer Worldwide. PloS one. 2016;11:e0159140.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  207. Syrjanen K. Geographic origin is a significant determinant of human papillomavirus prevalence in oesophageal squamous cell carcinoma: systematic review and meta-analysis. Scand J Infect Dis. 2013;45:1–18.

    Article  PubMed  Google Scholar 

  208. Syrjänen KJ. HPV infections and oesophageal cancer. J Clin Pathol. 2002;55:721–8.

    Article  PubMed  PubMed Central  Google Scholar 

  209. Pantham G, Ganesan S, Einstadter D, Jin G, Weinberg A, Fass R. Assessment of the incidence of squamous cell papilloma of the esophagus and the presence of high-risk human papilloma virus. Dis Esophagus. 2017;30:1–5.

    PubMed  Google Scholar 

  210. Gorgoulis V, Rassidakis G, Karameris A, Giatromanolaki A, Barbatis C, Kittas C. Expression of p53 protein in laryngeal squamous cell carcinoma and dysplasia: possible correlation with human papillomavirus infection and clinicopathological findings. Virchows Arch. 1994;425:481–9.

    Article  CAS  PubMed  Google Scholar 

  211. Hasegawa M, Ohoka I, Yamazaki K, Hanami K, Sugano I, Nagao T, Asoh A, Wada N, Nagao K, Ishida Y. Expression of p21/WAF-1, status of apoptosis and p53 mutation in esophageal squamous cell carcinoma with HPV infection. Pathol Int. 2002;52:442–50.

    Article  CAS  PubMed  Google Scholar 

  212. Sur M, Cooper K. The role of the human papilloma virus in esophageal cancer. Pathol. 1998;30:348–54.

    Article  CAS  Google Scholar 

  213. Zang B, Huang G, Wang X, Zheng S. HPV-16 E6 promotes cell growth of esophageal cancer via downregulation of miR-125b and activation of Wnt/beta-catenin signaling pathway. Int J Clin Exp Pathol. 2015;8:13687–94.

    PubMed  PubMed Central  Google Scholar 

  214. Patel K, Mining S, Wakhisi J, Gheit T, Tommasino M, Martel-Planche G, Hainaut P, Abedi-Ardekani B. TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya. BMC Res Notes. 2011;4:469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the staff of Eldoret Cancer Registry for providing updated records on the cancer prevalence in Uasin Gishu District.

Funding

The study received no funding.

Availability of data and materials

All available data are included in the article text.

Open Access

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Author information

Authors and Affiliations

Authors

Contributions

GK prepared the draft manuscript. NB, ZK, HR, WK and EJ acquired the data. GK, NB, ZK and EJ analyzed the data. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Gabriel Kigen.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kigen, G., Busakhala, N., Kamuren, Z. et al. Factors associated with the high prevalence of oesophageal cancer in Western Kenya: a review. Infect Agents Cancer 12, 59 (2017). https://doi.org/10.1186/s13027-017-0169-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13027-017-0169-y

Keywords