A very-hot food and beverage thermal exposure index and esophageal cancer risk in Malawi and Tanzania: findings from the ESCCAPE case-control studies.

BACKGROUND: Consumption of very-hot beverages/food is a probable carcinogen. In East Africa, we investigated esophageal squamous cell carcinoma (ESCC) risk in relation to four thermal exposure metrics separately and in a combined score. METHODS: From the ESCCAPE case-control studies in Blantyre, Malawi (2017-20) and Kilimanjaro, Tanzania (2015-19), we used logistic regression models adjusted for country, age, sex, alcohol and tobacco, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported thermal exposures whilst consuming tea, coffee and/or porridge. RESULTS: The study included 849 cases and 906 controls. All metrics were positively associated with ESCC: temperature of drink/food (OR 1.92 (95% CI: 1.50, 2.46) for 'very hot' vs 'hot'), waiting time before drinking/eating (1.76 (1.37, 2.26) for <2 vs 2-5 minutes), consumption speed (2.23 (1.78, 2.79) for 'normal' vs 'slow') and mouth burning (1.90 (1.19, 3.01) for ≥6 burns per month vs none). Amongst consumers, the composite score ranged from 1 to 12, and ESCC risk increased with higher scores, reaching an OR of 4.6 (2.1, 10.0) for scores of ≥9 vs 3. CONCLUSIONS: Thermal exposure metrics were strongly associated with ESCC risk. Avoidance of very-hot food/beverage consumption may contribute to the prevention of ESCC in East Africa.

Alcohol consumption and oesophageal squamous cell cancer risk in east Africa: findings from the large multicentre ESCCAPE case-control study in Kenya, Tanzania, and Malawi.

BACKGROUND: The contribution of alcohol to the large burden of oesophageal squamous cell carcinoma (ESCC) in east Africa remains uncertain and difficult to assess owing to complex consumption patterns of traditional and commercial drinks. We aimed to assess whether alcohol drinking, overall and at specific intake levels, contributes to ESCC risk in east Africa. METHODS: We did a hospital-based case-control study in Kenya, Tanzania, and Malawi, which included comprehensive assessment of a variety of locally consumed alcohol that we used to classify drinkers as exclusively low alcohol-by-volume (ABV; <30% ABV) drinkers or drinkers of some high-ABV drinks, as well as the number of drinks consumed, average weekly ethanol intake, and the contribution of each drink type to overall ethanol consumption. Cases were patients aged 18 years and older with incident primary ESCC, confirmed histologically for the majority of cases, and a clinical diagnosis for the remainder. Controls were frequency-matched on age and sex in a 1:1 ratio with cases. The controls were recruited from the same hospitals as cases and included outpatients, inpatients, and hospital visitors who did not have cancer or any other digestive disease. Consenting participants took part in face-to-face interviews in which they were asked whether they had ever consumed alcohol (the primary exposure variable); those who had were asked follow-up questions about their consumption habits for different alcoholic drinks. FINDINGS: 1279 cases and 1346 controls were recruited between Aug 5, 2013, and May 24, 2020, including 430 cases and 440 controls from Kenya, 310 cases and 313 controls from Tanzania, and 539 cases and 593 controls from Malawi. 65 (4·8%) of 1344 cases were excluded. Consistent positive associations with ESCC risk were found for ever having consumed alcohol in Kenyan men and Tanzanian men, and for daily number of drinks and estimated ethanol intake in Kenya, Tanzania (both sexes) and Malawian women. Corresponding population-attributable fractions of ESCC for those reporting ever drinking alcohol (vs never drinking) were 65% (95% CI 52-78) in Kenyan men and 23% (<1-45) in Kenyan women, and 56% (95% CI 36-76) in Tanzanian men and 5% (0-42) in Tanzanian women. Increased risk and population-attributable fractions were almost entirely due to risks in high-ABV drinkers. INTERPRETATION: Alcohol appears to be a substantial contributor to ESCC risk in east Africa, particularly among men, and a large fraction of ESCC could be prevented by cessation or reduction of alcohol consumption. Future studies should consider independent ascertainment of alcohol intake to assess the potential of under-reporting in Malawi. FUNDING: US National Cancer Institute, Wereld Kanker Onderzoek Fonds, and the IARC Environment and Lifestyle Epidemiology Branch. TRANSLATIONS: For the Swahili and Chichewa translations of the abstract see Supplementary Materials section.

Surveillance of premalignant gastric cardia lesions: A population-based prospective cohort study in China.

In our study, we aimed to assess the long-term risk of gastric cardia adenocarcinoma (GCA) for patients with different histological cardia lesions to inform future guidelines for GCA screening in China. We conducted a population-based prospective study among 9740 subjects who underwent upper endoscopy screening during 2005 to 2009 and followed until December 2017. Cumulative incidence and mortality rates of GCA were calculated by the baseline histological diagnoses, and the hazard ratios (HRs), overall and by age and sex, were analyzed by Cox proportional hazards models. During a median follow-up of 10 years, we identified 123 new GCA cases (1.26%) and 31 GCA deaths (0.32%). The age-standardized incidence and mortality rates of GCA were 128.71/100 000 and 35.69/100 000 person-years, and cumulative incidence rate in patients with cardia high-grade dysplasia (CHGD), cardia low-grade dysplasia (CLGD) and atrophic carditis (AC)/cardia intestinal metaplasia (CIM) was 25%, 3.05% and 1.58%, respectively. The progression rate and cancer risk of GCA increased monotonically with each step in Correa's cascade. Individuals aged 50 to 69 years had 4.4 times higher GCA incidence than those aged 40 to 49 years. Patients with CLGD had a significantly higher 3-year GCA incidence than the normal group, while patients with AC/CIM had a comparable GCA risk during 3-year follow-up but a higher risk at 5-year intervals. Our results suggested a postponed starting age of 50 years for GCA screening, immediate treatment for patients with CHGD, a 3-year surveillance interval for patients with CLGD, and a lengthened surveillance interval of 5 years for patients with AC/CIM.

Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers.

Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δß) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. SIGNIFICANCE: This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/10/2612/F1.large.jpg.

Missing and decayed teeth, oral hygiene and dental staining in relation to esophageal cancer risk: ESCCAPE case-control study in Kilimanjaro, Tanzania.

In the African esophageal squamous cell carcinoma (ESCC) corridor, recent work from Kenya found increased ESCC risk associated with poor oral health, including an ill-understood association with dental fluorosis. We examined these associations in a Tanzanian study, which included examination of potential biases influencing the latter association. This age and sex frequency-matched case-control study included 310 ESCC cases and 313 hospital visitor/patient controls. Exposures included self-reported oral hygiene and nondental observer assessed decayed+missing+filled tooth count (DMFT index) and the Thylstrup-Fejerskov dental fluorosis index (TFI). Blind to this nondental observer TFI, a dentist independently assessed fluorosis on photographs of 75 participants. Odds ratios (ORs) are adjusted for demographic factors, alcohol and tobacco. ESCC risk was associated with using a chewed stick to brush teeth (OR 2.3 [95% CI: 1.3-4.1]), using charcoal to whiten teeth (OR 2.13 [95% CI: 1.3, 4.1]) and linearly with the DMFT index (OR 3.3 95% CI: [1.8, 6.0] for ≥10 vs 0). Nondental observer-assessed fluorosis was strongly associated with ESCC risk (OR 13.5 [95% CI: 5.7-31.9] for TFI 5+ v 0). However, the professional dentist's assessment indicated that only 43% (10/23) of participants assessed as TFI 5+ actually had fluorosis. In summary, using oral charcoal, brushing with a chewed stick and missing/decayed teeth may be risk factors for ESCC in Tanzania, for which dose-response and mechanistic research is needed. Links of ESCC with "dental fluorosis" suffered from severe exposure misclassification, rendering it impossible to disentangle any effects of fluorosis, extrinsic staining or reverse causality.

Minimally invasive esophageal sponge cytology sampling is feasible in a Tanzanian community setting.

Esophageal sponge cytology is an endoscopy alternative well accepted by patients with extensive data for accuracy in the context of adenocarcinoma. Few studies have assessed its feasibility in asymptomatic community members, and fewer still in East Africa, where esophageal squamous cell carcinoma (ESCC) rates are high. We aimed to assess the feasibility of a capsule-based diagnosis of esophageal squamous dysplasia (ESD), an ESCC precursor, which may benefit epidemiological and early detection research. We collected Cytosponge collections in 102 asymptomatic adults from Kilimanjaro, Tanzania. Uptake, acceptability and safety were assessed. Participants scored acceptability immediately following the procedure and 7 days later on a scale of 0 (least) to 10 (most acceptable). Slides from paraffin-embedded cell clots were read by two pathologists for ESD and other pathologies. All participants (52 men, 50 women, aged 30-77) swallowed the device at first attempt, 100 (98%) of which gave slides of adequate cellularity. Acceptability scores were 10 (53%), 9 (24%), 8 (21%), 7 (2%) and 6 (1%), with no differences by age, sex or time of asking. Cytological findings were esophageal inflammation (4%), atypical squamous cells of uncertain significance (1%), low-grade dysplasia (1%), gastritis (22%) and suspected intestinal metaplasia (6%). Setting-specific logistical and ethical considerations of study implementation are discussed. We demonstrate the safety, acceptability and feasibility of Cytosponge sampling in this setting, paving the way for innovative etiology and early-detection research. Targeted sampling strategies and biomarker development will underpin the success of such initiatives. The study protocol is registered on ClinicalTrials.gov (NCT04090554).

Helicobacter pylori Is Associated With Precancerous and Cancerous Lesions of the Gastric Cardia Mucosa: Results of a Large Population-Based Study in China.

Background: Helicobacter pylori (H. pylori) is widely accepted to be the most important cause of gastric non-cardia adenocarcinoma (GNCA), while its role in the development of gastric cardia adenocarcinoma (GCA) is not well-defined. We aimed to investigate current H. pylori infection in relation to the severity of both precancerous and cancerous lesions of the gastric cardia in an Asian population at high risk of GCA. Methods: A population-based cross-sectional study was conducted in Linzhou County, Henan Province, China. Two thousand three (2,003) randomly selected participants with data on current H. pylori infection, assayed by 13C-urea breath test (13C-UBT), and a sequence of histological diagnoses of the gastric cardia mucosa were analyzed. Results: Of 2,003 subjects, 828 (41.33%) were currently infected with H. pylori. The prevalence of current H. pylori infection increased with increasing severity of histological lesions, from 34.12% in subjects with normal gastric cardia mucosa to 52.17% in subjects with gastric cardia high-grade intraepithelial neoplasia (CHIN)/ gastric cardia adenocarcinoma (GCA) (P for trend <0.001). With H. pylori-negative subjects as the reference category, H. pylori-positive subjects had statistically significant elevated adjusted prevalence odds ratios (PORs) for each of the histological lesions. The PORs (95% CI) were 2.15 (1.74-2.64), 3.46 (2.08-5.75), 2.78 (1.90-4.07), and 3.05 (1.30-7.17) for subjects with carditis, cardia intestinal metaplasia (CIM), cardia low-grade intraepithelial neoplasia (CLIN), and CHIN/GCA), respectively. The associations remained when subjects with abnormal stomach non-cardia mucosa were excluded. Conclusions: This large epidemiologic study demonstrates a positive association between current H. pylori infection and the severity of both precancerous and cancerous lesions of the gastric cardia in an Asian population at high risk of GCA. These findings suggest that H. pylori infection may play a role throughout both early- and late-stage development of GCA.

Environmental geochemistry and cancer: a pertinent global health problem requiring interdisciplinary collaboration.

Primary prevention is a key strategy to reducing the global burden of cancer, a disease responsible for ~ 9.6 million deaths per year and predicted to top 13 million by 2030. The role of environmental geochemistry in the aetiology of many cancers-as well as other non-communicable diseases-should not be understated, particularly in low- and middle-income countries where 70% of global cancer deaths occur and reliance on local geochemistry for drinking water and subsistence crops is still widespread. This article is an expansion of a series of presentations and discussions held at the 34th International Conference of the Society for Environmental Geochemistry and Health in Livingstone, Zambia, on the value of effective collaborations between environmental geochemists and cancer epidemiologists. Key technical aspects of each field are presented, in addition to a case study of the extraordinarily high incidence rates of oesophageal cancer in the East African Rift Valley, which may have a geochemical contribution. The potential merit of veterinary studies for investigating common geochemical risk factors between human and animal disease is also highlighted.

Iodine status in western Kenya: a community-based cross-sectional survey of urinary and drinking water iodine concentrations.

Spot urinary iodine concentrations (UIC) are presented for 248 individuals from western Kenya with paired drinking water collected between 2016 and 2018. The median UIC was 271 µg L-1, ranging from 9 to 3146 µg L-1, unadjusted for hydration status/dilution. From these data, 12% were potentially iodine deficient (< 100 µg L-1), whilst 44% were considered to have an excess iodine intake (> 300 µg L-1). The application of hydration status/urinary dilution correction methods was evaluated for UICs, using creatinine, osmolality and specific gravity. The use of specific gravity correction for spot urine samples to account for hydration status/urinary dilution presents a practical approach for studies with limited budgets, rather than relying on unadjusted UICs, 24 h sampling, use of significantly large sample size in a cross-sectional study and other reported measures to smooth out the urinary dilution effect. Urinary corrections did influence boundary assessment for deficiency-sufficiency-excess for this group of participants, ranging from 31 to 44% having excess iodine intake, albeit for a study of this size. However, comparison of the correction methods did highlight that 22% of the variation in UICs was due to urinary dilution, highlighting the need for such correction, although creatinine performed poorly, yet specific gravity as a low-cost method was comparable to osmolality corrections as the often stated 'gold standard' metric for urinary concentration. Paired drinking water samples contained a median iodine concentration of 3.2 µg L-1 (0.2-304.1 µg L-1). A weak correlation was observed between UIC and water-I concentrations (R = 0.11).

Urine selenium concentration is a useful biomarker for assessing population level selenium status.

Plasma selenium (Se) concentration is an established population level biomarker of Se status, especially in Se-deficient populations. Previously observed correlations between dietary Se intake and urinary Se excretion suggest that urine Se concentration is also a potentially viable biomarker of Se status. However, there are only limited data on urine Se concentration among Se-deficient populations. Here, we test if urine is a viable biomarker for assessing Se status among a large sample of women and children in Malawi, most of whom are likely to be Se-deficient based on plasma Se status. Casual (spot) urine samples (n = 1406) were collected from a nationally representative sample of women of reproductive age (WRA, n =741) and school aged children (SAC, n=665) across Malawi as part of the 2015/16 Demographic and Health Survey. Selenium concentration in urine was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary dilution corrections for specific gravity, osmolality, and creatinine were applied to adjust for hydration status. Plasma Se status had been measured for the same survey participants. There was between-cluster variation in urine Se concentration that corresponded with variation in plasma Se concentration, but not between households within a cluster, or between individuals within a household. Corrected urine Se concentrations explained more of the between-cluster variation in plasma Se concentration than uncorrected data. These results provide new evidence that urine may be used in the surveillance of Se status at the population level in some groups. This could be a cost-effective option if urine samples are already being collected for other assessments, such as for iodine status analysis as in the Malawi and other national Demographic and Health Surveys.

Source apportionment of micronutrients in the diets of Kilimanjaro,Tanzania and Counties of Western Kenya.

Soil, water and food supply composition data have been combined to primarily estimate micronutrient intakes and subsequent risk of deficiencies in each of the regions studied by generating new data to supplement and update existing food balance sheets. These data capture environmental influences, such as soil chemistry and the drinking water sources to provide spatially resolved crop and drinking water composition data, where combined information is currently limited, to better inform intervention strategies to target micronutrient deficiencies. Approximately 1500 crop samples were analysed, representing 86 food items across 50 sites in Tanzania in 2013 and >230 sites in Western Kenya between 2014 and 2018. Samples were analysed by ICP-MS for 58 elements, with this paper focussing on calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), iodine (I), zinc (Zn) and molybdenum (Mo). In general, micronutrient supply from food groups was higher from Kilimanjaro,Tanzania than Counties in Western Kenya, albeit from a smaller sample. For both countries leafy vegetable and vegetable food groups consistently contained higher median micronutrient concentrations compared to other plant based food groups. Overall, calculated deficiency rates were <1% for Cu and Mo and close to or >90% for Ca, Zn and I in both countries. For Mg, a slightly lower risk of deficiency was calculated for Tanzania at 0 to 1% across simplified soil classifications and for female/males, compared to 3 to 20% for Kenya. A significant difference was observed for Se, where a 3 to 28% risk of deficiency was calculated for Tanzania compared to 93 to 100% in Kenya. Overall, 11 soil predictor variables, including pH and organic matter accounted for a small proportion of the variance in the elemental concentration of food. Tanzanian drinking water presented several opportunities for delivering greater than 10% of the estimated average requirement (EAR) for micronutrients. For example, 1 to 56% of the EAR for I and up to 10% for Se or 37% for Zn could be contributed via drinking water.

Esophageal Thermal Exposure to Hot Beverages: A Comparison of Metrics to Discriminate Distinct Consumption Habits.

BACKGROUND: Hot beverage consumption is a probable risk factor for esophageal squamous cell carcinoma (ESCC). No standardized exposure assessment protocol exists. METHODS: To compare how alternative metrics discriminate distinct drinking habits, we measured sip temperatures and sizes in an international group of hot beverage drinkers in France (n = 20) and hot porridge consumers (n = 52) in a high ESCC incidence region of China. Building on the knowledge that sip size and temperature affect intraesophageal liquid temperature (IELT), IELTs were predicted by modeling existing data, and compared with first sip temperature and, across all sips, mean temperature and sip-weighted mean temperature. RESULTS: Two contrasting exposure characteristics were observed. Compared with the international group, Chinese porridge consumers took larger first sips [mean difference +17 g; 95% confidence interval (CI), 13.3-20.7] of hotter (+9.5°C; 95% CI, 6.2-12.7) liquid, and their mean sip size did not vary greatly across sips, but the former groups increased in size as temperature decreased. This resulted in higher predicted IELTs (mean 61°C vs. 42.4°C) and sip-weighted temperatures (76.9°C vs. 56°C) in Chinese porridge consumers, and compared with first sip and mean temperature, these two metrics separated the groups to a greater extent. CONCLUSIONS: Distinguishing thermal exposure characteristics between these groups was greatly enhanced by measuring sip sizes. Temperature at first sip alone is suboptimal for assessing human exposure to hot foods and beverages, and future studies should include sip size measurements in exposure assessment protocols. IMPACT: This study provides a logistically feasible framework for assessing human exposure to hot beverages.

A comparative assessment of dilution correction methods for spot urinary analyte concentrations in a UK population exposed to arsenic in drinking water.

Spot urinary concentrations of environmental exposure biomarkers require correction for dilution. There is no consensus on the most appropriate method, with creatinine used by default despite lacking theoretical robustness. We comparatively assessed the efficacy of creatinine; specific gravity (SG); osmolality and modifications of all three for dilution correcting urinary arsenic. For 202 participants with urinary arsenic, creatinine, osmolality and SG measurements paired to drinking water As, we compared the performance corrections against two independent criteria: primarily, (A) correlations of corrected urinary As and the dilution measurements used to correct them - weak correlations indicating good performance and (B) correlations of corrected urinary As and drinking water As - strong correlations indicating good performance. More than a third of variation in spot urinary As concentrations was attributable to dilution. Conventional SG and osmolality correction removed significant dilution variation from As concentrations, whereas conventional creatinine over-corrected, and modifications of all three removed measurable dilution variation. Modified creatinine and both methods of SG and osmolality generated stronger correlations of urinary and drinking water As concentrations than conventional creatinine, which gave weaker correlations than uncorrected values. A disparity in optima between performance criteria was observed, with much smaller improvements possible for Criterion B relative to A. Conventional corrections - particularly creatinine - limit the utility spot urine samples, whereas a modified technique outlined here may allow substantial improvement and can be readily retrospectively applied to existing datasets. More studies are needed to optimize urinary dilution correction methods. Covariates of urinary dilution measurements still warrant consideration.

Intra-household agreement of urinary elemental concentrations in Tanzania and Kenya: potential surrogates in case-control studies.

Element deficiencies and excesses play important roles in non-communicable disease aetiology. When investigating their roles in epidemiologic studies without prospective designs, reverse-causality limits the utility of transient biomarkers in cases. This study aimed to investigate whether surrogate participants may provide viable proxies by assessing concentration correlations within households. We obtained spot urine samples from 245 Tanzanian and Kenyan adults (including 101 household pairs) to investigate intra-household correlations of urinary elements (As, Ba, Ca, Cd, Co, Cs, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, S, Se, Sr, Tl, V and Zn) and concentrations (also available for: Bi, Ce, Sb, Sn and U) relative to external population-levels and health-based values. Moderate-strong correlations were observed for As (r = 0.65), Cs (r = 0.67), Li (r = 0.56), Mo (r = 0.57), Se (r = 0.68) and Tl (r = 0.67). Remaining correlations were <0.41. Median Se concentrations in Tanzania (29 µg/L) and Kenya (24 µg/L) were low relative to 5738 Canadians (59 µg/L). Exceedances (of reference 95th percentiles) were observed for: Co, Mn, Mo, Ni and U. Compared to health-based values, exceedances were present for As, Co, Mo and Se but deficiencies were also present for Mo and Se. For well correlated elements, household members in East African settings provide feasible surrogate cases to investigate element deficiencies/excesses in relation to non-communicable diseases.

Traditional and commercial alcohols and esophageal cancer risk in Kenya.

Squamous cell esophageal cancer is common throughout East Africa, but its etiology is poorly understood. We investigated the contribution of alcohol consumption to esophageal cancer in Kenya, based on a hospital-based case-control study conducted from 08/2013 to 03/2018 in Eldoret, western Kenya. Cases had an endoscopy-confirmed esophageal tumor whose histology did not rule out squamous cell carcinoma. Age and gender frequency-matched controls were recruited from hospital visitors/patients without digestive diseases. Logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CI) adjusting for tobacco (type, intensity) and 6 other potential confounders. A total of 422 cases (65% male, mean at diagnosis 60 (SD 14) years) and 414 controls were included. ORs for ever-drinking were stronger in ever-tobacco users (9.0, 95% CI: 3.4, 23.8, with few tobacco users who were never drinkers) than in never-tobacco users (2.6, 95% CI: 1.6, 4.1). Risk increased linearly with number of drinks: OR for >6 compared to >0 to ≤2 drinks/day were 5.2 (2.4, 11.4) in ever-tobacco users and 2.1 (0.7, 4.4) in never-tobacco users. Although most ethanol came from low ethanol alcohols (busaa or beer), for the same ethanol intake, if a greater proportion came from the moonshine chang'aa, it was associated with a specific additional risk. The population attributable fraction for >2 drinks per day was 48% overall and highest in male tobacco users. Alcohol consumption, particularly of busaa and chang'aa, contributes to half of the esophageal cancer burden in western Kenya.

Hot beverages and oesophageal cancer risk in western Kenya: Findings from the ESCCAPE case-control study.

Oesophageal squamous cell carcinoma (ESCC) has markedly high incidence rates in Kenya and much of East Africa, with a dire prognosis and poorly understood aetiology. Consumption of hot beverages-a probable carcinogen to humans-is associated with increased ESCC risk in other settings and is habitually practiced in Kenya. We conducted a case-control study in Eldoret, western Kenya between August 2013 and March 2018. Cases were patients with endoscopically confirmed oesophageal cancer whose histology did not rule out ESCC. Age and sex-matched controls were hospital visitors and hospital out and in-patients excluding those with digestive diseases. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for self-reported drinking temperatures; consumption frequency; mouth burning frequency and hot porridge consumption using logistic regression models adjusted for potential confounders. Drinking temperature association with tumour sub-location was also investigated. The study included 430 cases and 440 controls. Drinkers of 'very hot' and 'hot' beverages (>95% tea) had a 3.7 (95% CI: 2.1-6.5) and 1.4-fold (1.0-2.0) ESCC risk, respectively compared to 'warm' drinkers. This trend was consistent in males, females, never and ever alcohol/tobacco and was stronger over than under age 50 years. The tumour sub-location distribution (upper/middle/lower oesophagus) did not differ by reported drinking temperature. Our study is the first comprehensive investigation in this setting to-date to observe a link between hot beverage consumption and ESCC in East Africa. These findings provide further evidence for the role of this potentially modifiable risk factor in ESCC aetiology.

Dental fluorosis and oral health in the African Esophageal Cancer Corridor: Findings from the Kenya ESCCAPE case-control study and a pan-African perspective.

There are no studies of oral health in relation to esophageal cancer in Africa, or of Eastern Africa's endemic dental fluorosis, an irreversible enamel hypo-mineralization due to early-life excessive fluoride intake. During 2014-18, we conducted a case-control study of squamous cell esophageal cancer in Eldoret, western Kenya. Odds ratios (AORs (95% confidence intervals)) were adjusted for design factors, tobacco, alcohol, ethnicity, education, oral hygiene and missing/decayed teeth. Esophageal cancer cases (N = 430) had poorer oral health and hygiene than controls (N = 440). Compared to no dental fluorosis, moderate/severe fluorosis, which affected 44% of cases, had a crude OR of 20.8 (11.6, 37.4) and on full adjustment was associated with 9.4-fold (4.6, 19.1) increased risk, whilst mild fluorosis (43% of cases) had an AOR of 2.3 (1.3, 4.0). The prevalence of oral leukoplakia and tooth loss/decay increased with fluorosis severity, and increased cancer risks associated with moderate/severe fluorosis were particularly strong in individuals with more tooth loss/decay. Using a mswaki stick (AOR = 1.7 (1.0, 2.9)) rather than a commercial tooth brush and infrequent tooth brushing also independently increased risk. Geographic variations showed that areas of high esophageal cancer incidence and those of high groundwater fluoride levels have remarkably similar locations across Eastern Africa. In conclusion, poor oral health in combination with, or as a result of, high-altitude susceptibility to hydro-geologically influenced dental fluorosis may underlie the striking co-location of Africa's esophageal cancer corridor with the Rift Valley. The findings call for heightened research into primary prevention opportunities of this highly fatal but common cancer.