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.

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.

BackgroundThere are numerous methods for adjusting measured concentrations of urinary biomarkers for hydration variation. Few studies use objective criteria to quantify the relative performance of these methods. Our aim was to compare the performance of existing methods for adjusting urinary biomarkers for hydration variation.MethodsCreatinine, osmolality, excretion rate (ER), bodyweight adjusted ER (ERBW) and empirical analyte-specific urinary flow rate (UFR) adjustment methods on spot urinary concentrations of lead (Pb), cadmium (Cd), non-arsenobetaine arsenic (AsIMM) and iodine (I) from the US National Health and Nutrition Examination Survey (NHANES) (2009–2010 and 2011–2012) were evaluated. The data were divided into a training dataset (n = 1,723) from which empirical adjustment coefficients were derived and a testing dataset (n = 428) on which quantification of the performance of the adjustment methods was done by calculating, primarily, the correlation of the adjusted parameter with UFR, with lower correlations indicating better performance and, secondarily, the correlation of the adjusted parameters with blood analyte concentrations (Pb and Cd), with higher correlations indicating better performance.ResultsOverall performance across analytes was better for Osmolality and UFR based methods. Excretion rate and ERBW consistently performed worse, often no better than unadjusted concentrations.ConclusionsOsmolality adjustment of urinary biomonitoring data provides for more robust adjustment than either creatinine based or ER or ERBW methods, the latter two of which tend to overcompensate for UFR. Modified UFR methods perform significantly better than all but osmolality in removing hydration variation, but depend on the accuracy of UFR calculations. Hydration adjustment performance is analyte-specific and further research is needed to establish a robust and consistent framework.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0152-x) contains supplementary material, which is available to authorized users.

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.

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Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.

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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.