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In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case-cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26-2.14, and 1.60; 1.15-2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88-1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies. [ABSTRACT FROM AUTHOR]

Background: Oesophageal squamous cell carcinoma (05CC) has a very poor prognosis, which is largely due to late diagnosis. Successful early detection strategies will require identification of clinically relevant precursor lesions that can be targets for screening and treatment. Aims: To identify the clinically relevant histological precursors of OSCC. Subjects: A cohort of 682 endoscoped patients from a high risk rural population in Linxian, China. Methods: Subjects were endoscoped and biopsied at baseline and followed for 13.5 years. We estimated the relative risk of developing OSCC for each of the initial histological diagnoses using Cox proportional hazards regression models. Results: A total of 114 (16.7%) patients developed OSCC during the follow up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for incidence of this tumour, by initial histological diagnosis, were: normal 1.0 (reference), oesophagitis 0.8 (0.2-3.2), basal cell hyperplasia 1.9 (0.8-4.5), mild dysplasia 2.9 (1.6-5.2), moderate dysplasia 9.8 (5.3-18.3), severe dysplasia 28.3 (15.3-52.3), and carcinoma in situ 34.4 (16.6-71.4). Conclusions: In this study, squamous dysplasia and carcinoma in situ were the only histological lesions associated with a significantly increased risk of developing OSCC within 13.5 years after endoscopy. There was no evidence that oesophagitis predisposed to this tumour. Increasing grades of dysplasia were strongly associated with increasing risk indicating that the histological grading was clinically meaningful. The follow up experience of severe dysplasia and carcinoma in situ was equivalent, suggesting that this distinction is not clinically relevant. Documenting these precursor lesions of OSCC should assist in the development of effective prevention, early detection, and treatment strategies for this disease. [ABSTRACT FROM AUTHOR]

To investigate the incidence of oesophageal cancer (EC) in the Golestan province of North-East Iran, we invited 1349 rural and urban inhabitants of Golestan province aged 35-80 to undergo extensive lifestyle interviews and to provide biological samples. The interview was repeated on a subset of 130 participants to assess reliability of questionnaire and medical information. Temperature at which tea was consumed was measured on two occasions by 110 subjects. Samples of rice, wheat and sorghum were tested for fumonisin contamination. An active follow-up was carried out after 6 and 12 months. A total of 1057 subjects (610 women and 447 men) participated in this feasibility study (78.4% participation rate). Cigarette smoking, opium and alcohol use were reported by 163 (13.8%), 93 (8.8%) and 39 (3.7%) subjects, respectively. Tobacco smoking was correlated with urinary cotinine (kappa = 0.74). Most questionnaire data had kappa > 0.7 in repeat measurements; tea temperature measurement was reliable (kappa = 0.71). No fumonisins were detected in the samples analysed. During the follow-up six subjects were lost (0.6%), two subjects developed EC (one dead, one alive); in all, 13 subjects died (with cause of death known for 11, 84.6%). Conducting a cohort study in Golestan is feasible with reliable information obtained for suspected risk factors; participants can be followed up for EC incidence and mortality. [ABSTRACT FROM AUTHOR]

Dynamic material properties of the tectorial membrane (TM) have been measured at audio frequencies in TMs excised from the apical portions of mouse cochleae. We review, integrate, and interpret recent findings. The mechanical point impedance of the TM in the radial, longitudinal, and transverse directions is viscoelastic and has a frequency dependence of the form 1/(K(j2πf)α) for 10≤f≤4000 Hz, where f is frequency, K is a constant, j=−1, and α≈0.66. Comparison with other connective tissues shows that the TM is a relatively lossy viscoelastic material. The median magnitudes of the point impedance at 10 Hz in the radial, longitudinal, and transverse directions are 4.6×10−3 N·s/m, 1.8×10−3 N·s/m, and 2.7×10−3 N·s/m. Consistent with osmotic responses (Freeman et al., 2003), the TM point impedance is anisotropic – the TM is stiffer in the radial than in the longitudinal and transverse directions. The mechanical space constant of the TM is approximately 20 μm. Comparisons reveal that in the apical region of the mouse cochlea, the TM dynamic stiffness at 10 Hz is 10 times larger than the static stiffness of the aggregate hair cells in a mechanical space constant and roughly comparable to the stiffness of the basilar membrane. We conclude that the TM provides a mechanical load on the basilar membrane and that the lability of the TM to changes in endolymph composition may well be reflected in changes in basilar membrane motion. [Copyright &y& Elsevier]

Objective: To determine the association between tooth loss and the risk of developing esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, or gastric non-cardia adenocarcinoma in a prospective study.Methods: Cox proportional hazards regression was used to examine these associations in a 28,868-person cohort followed prospectively for 5.25 years. The baseline questionnaire included questions regarding tooth loss, and individuals reporting lost teeth had their teeth counted by study personnel. The analytic cohort included 620 esophagus, 431 gastric cardia, and 102 gastric non-cardia cancer cases.Results: Tooth loss was associated with a significantly elevated risk of developing all three cancers. When examined as median splits, tooth loss was associated with a relative risk (RR) (95% confidence interval, CI) of 1.3 (1.1-1.6) in the esophagus, 1.3 (1.0-1.6) in the gastric cardia, and 1.8 (1.1-3.0) in the gastric non-cardia. Further analysis demonstrated that this increased risk was most strongly associated with the loss of the first few teeth and was primarily confined to the younger members of our cohort.Conclusions: In this cohort tooth loss increased the risk of developing upper gastrointestinal cancer. We hypothesize that this may be related to alterations in oral bacterial flora and subsequent increases in the in-vivo production of carcinogens such as nitrosamines. [ABSTRACT FROM AUTHOR]

Objective: Ecologic studies of esophageal squamous cell carcinoma (ESCC) have reported an association with consumption of maize contaminated with Fusarium verticillioides, which produce fungal toxins referred to as fumonisins. Fumonisins disrupt sphingolipid metabolism and serum sphingolipids have been proposed as biomarkers of fumonisin exposure. We conducted a prospective nested case-control study to examine the relationship between serum sphingolipids and ESCC incidence.Methods: Cases and controls were selected from a large prospective trial conducted in Linxian, People's Republic of China. Ninety-eight ESCC cases were randomly selected from the 639 incident ESCC ascertained during the initial 5.25 years of follow-up: 185 controls were also randomly selected based on the distribution of cases among six age and sex strata. Concentrations of sphinganine and sphingosine were determined by high-performance liquid chromatography in serum collected at the study baseline.Results: No significant associations were found between serum sphingosine, sphinganine, or the sphinganine/ sphingosine ratio and ESCC incidence in conditional and unconditional logistic regression models with adjustment for age, sex, tobacco use. and alcohol use.Conclusion: Our study is the first prospective study to assess the relationship between sphingolipid levels, as biomarkers of fumonisin exposure, and cancer incidence. We found no significant association between sphingolipid levels and risk of ESCC. [ABSTRACT FROM AUTHOR]

Sphinganine and sphingosine, the two sphingoid base backbones of sphingolipids, are highly bioactive compounds that are of increasing interest to nutritionists because they occur in food and their metabolism can be altered by fungal toxins that contaminate some foods. Nonetheless, no studies of diet and sphinganine or sphingosine concentrations in serum have yet been reported. Here we describe a cross-sectional study of 265 residents of Linxian, People's Republic of China, which examines potential demographic, physiologic and dietary correlates of serum sphinganine and sphingosine in this population. Median concentrations of serum sphinganine and sphingosine were compared among strata for 29 different variables. For sphinganine, no significant differences were found. For sphingosine, significant differences were seen among strata of age, menstruation status, serum cholesterol, carotenoids, retinol, tocopherols, fresh and dried vegetable and fresh fruit consumption. Using multivariate linear regression with stepwise selection, we found that the significant predictors for serum sphingosine included total tocopherols, age, serum selenium and retinol, with a final R(2) = 0.22; for sphinganine, tooth loss was the sole correlate, with R(2) = 0.015. Analyses using ranked sphingolipid data or principal components analysis, to simplify the food variables, did not materially alter these results. This study represents the largest report of human serum sphingolipid concentrations to date and provides insight into potential explanatory variables that can be incorporated into future studies. [ABSTRACT FROM AUTHOR]

Abstract Background The oral health status of rural residents in the People's Republic of China has not been extensively studied and the relationship between poor oral health and esophageal cancer (EC) is unclear. We aim to report the oral health status of adults participating in an EC screening study conducted in a rural high-risk EC area of China and to explore the relationship between oral health and esophageal dysplasia. Methods National Health and Nutrition Examination Survey (NHANES) oral health examination procedures and the Modified Gingival Index (MGI) were used in a clinical study designed to examine risk factors for esophageal cancer and to test a new esophageal cytology sampling device. This study was conducted in three rural villages in China with high rates of EC in 2002 and was a collaborative effort involving investigators from the National Institutes of Health and the Cancer Institute of the Chinese Academy of Medical Sciences. Results Nearly 17% of the study participants aged 40–67 years old were edentulous. Overall, the mean number of adjusted missing teeth (including third molars and retained dental roots) was 13.8 and 35% had 7 contacts or less. Women were more likely to experience greater tooth loss than men. The average age at the time of first tooth loss for those with no posterior functional contacts was approximately 41 years for men and 36 years for women. The mean DMFT (decayed, missing, and filled teeth) score for the study population was 8.5. Older persons, females, and individuals having lower educational attainment had higher DMFT scores. The prevalence of periodontal disease (defined as at least one site with 3 mm of attachment loss and 4 mm of pocket depth) was 44.7%, and 36.7% of the study participants had at least one site with 6 mm or more of attachment loss. Results from a parsimonious multivariate model indicate that participants with poor oral health wemore likely to have esophageal dysplasia (OR = 1.59; 95% CI 1.06, 2.39). Conclusion This report describes the first use of NHANES oral health protocols employed in a clinical study conducted outside of the United States. The extent and severity of poor oral health in this Chinese study group may be an important health problem and contributing factor to the prevalence of EC.

Abstract Background The highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern Brazil. Methods Two hundred healthy adults (half smokers, half non smokers, half male and half female) were recruited, given a standardized questionnaire, and asked to provide a urine sample for measurement of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite). Urine 1-OHPG concentrations were measured using immunoaffinity chromatography and synchronous fluorescence spectroscopy and urine cotinine was measured using a dipstick test. We examined factors associated with 1-OHPG concentration using Wilcoxon tests and multiple linear regression. Results Urine 1-hydroxypyrene glucuronide (1-OHPG) was successfully measured on 199 subjects. The median (interquartile range) of urine 1-OHPG in the 199 participants was 2.09 pmol/mL (0.51, 5.84). Tobacco smoke exposure and maté drinking were statistically significantly associated with higher urine 1-OHPG concentrations in the multivariate linear regression model. Conclusion Tobacco smoke and maté both contribute to high levels of benzo[a]pyrene exposure in the people of southern Brazil. This high PAH exposure may contribute to the high rates of ESCC observed in this population. The increased urine 1-OHPG concentrations associated with maté suggest that contaminants, not just thermal injury, may help explain the increased risk of ESCC previously reported for maté consumption.

Abstract Background North central China has some of the highest rates of esophageal squamous cell carcinoma in the world with cumulative mortality surpassing 20%. Mitochondrial DNA (mtDNA) accumulates more mutations than nuclear DNA and because of its high abundance has been proposed as a early detection device for subjects with cancer at various sites. We wished to examine the prevalence of mtDNA mutation and polymorphism in subjects from this high risk area of China. Methods We used DNA samples isolated from tumors, adjacent normal esophageal tissue, and blood from 21 esophageal squamous cell carcinoma cases and DNA isolated from blood from 23 healthy persons. We completely sequenced the control region (D-Loop) from each of these samples and used a PCR assay to assess the presence of the 4977 bp common deletion. Results Direct DNA sequencing revealed that 7/21 (33%, 95% CI = 17–55%) tumor samples had mutations in the control region, with clustering evident in the hyper-variable segment 1 (HSV1) and the homopolymeric stretch surrounding position 309. The number of mutations per subject ranged from 1 to 16 and there were a number of instances of heteroplasmy. We detected the 4977 bp 'common deletion' in 92% of the tumor and adjacent normal esophageal tissue samples examined, whereas no evidence of the common deletion was found in corresponding peripheral blood samples. Conclusions Control region mutations were insufficiently common to warrant attempts to develop mtDNA mutation screening as a clinical test for ESCC. The common deletion was highly prevalent in the esophageal tissue of cancer cases but absent from peripheral blood. The potential utility of the common deletion in an early detection system will be pursued in further studies.

Purpose: To investigate the risk factors for squamous-cell carcinoma of the conjunctiva (SCCC) and other eye cancers in the NIH-AARP Diet and Health Study. Methods: We estimated incidence rates and associations with age, sex, race/ethnicity and ultraviolet radiation using Cox proportional hazards models. Results: The incidence was 37.3 per 106 for all eye cancers (N = 178), 8.4 per 106 for SCCC (N = 40) and 28.9 per 106 for other eye cancers (N = 138). For all eye cancers, the incidence was lower in women than in men (hazard ratio [HR] = 0.38, 95% CI: 0.26, 0.55) and in persons aged ≤60 years than those aged >60 years (HR = 0.51, 95% CI: 0.36, 0.72). The incidence was higher, but not statistically significant, in those with an average net erythemal exposure >170 versus ≤170 (HR = 1.19, 95% CI: 0.88, 1.63) and lower in those residing at latitudes >35° versus ≤35° (HR = 0.81, 95% CI: 0.61, 1.09). The patterns were similar for SCCC in sex, age, race/ethnicity and average net erythemal exposure, but not statistically significant. Conclusion: The incidence of all eye cancers was associated with male sex and older age. The same patterns were observed for SCCC. The associations reported here might be surrogates of exposure to ultraviolet radiation, although more follow-up is needed to obtain precise results. [ABSTRACT FROM AUTHOR]

Objective: In the United States, cancer mortality rates continue to decline, yet geographic and racial disparities persist and are particularly evident in the Delta region, characterized by high economic distress and disease burden. We examined cancer mortality patterns by demographic groups across geographic region (Delta vs non-Delta) and investigated the influence of macro-level social determinants of health (SDoH) in cancer death., Study Design and Methods: This observational study included cancer death records of individuals aged ≥20 years from 2018 to 2021 in the United States. County-level characteristics were ascertained through the linkage of multiple national administrative and community surveys. We estimated age-standardized mortality rates (ASR) and rate ratios. We calculated the adjusted relative risks by county-level SDoH (geographic region, rurality, household income, income inequality, health insurance, and education) and other factors using age-adjusted multivariate quasi-Poisson regression., Results: In 2018-2021, approximately 2.4 million cancer deaths occurred in the United States. We observed important declines in the Black-White disparities, from 16.6% in 2018 (ASR = 289.9 vs 248.6 per 100,000) to 12.1% in 2021 (281.1 vs 250.8) in the Delta region and from 15.9% (254.9 vs 219.9) to 10.7% (240.6 vs 217.3) in the non-Delta region, though Black men in the Delta region remained the highest rate (ASR 2021  = 346.9 per 100,000). County-level analyses provided strong evidence of geographic inequality and the role of SDoH, particularly education and income inequality., Conclusions: Unfavorable SDoH are associated with increased cancer death risk. Region-specific health policies and interventions in the Delta region are essential to advance cancer health equity., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Evidence on the associations of body size and occupational physical activity (PA) during the life course with gastrointestinal cancers is inconclusive. We analyzed data from the Golestan Cohort Study, a population-based prospective cohort study from Iran, with 50,045 individuals aged 40-75 years enrolled during 2004-2008 and followed through April 2023. Body size during adolescence, early adulthood, and at cohort baseline was assessed using validated pictograms. Large adolescent body size was associated with total gastrointestinal cancers (hazard ratio, HR: 1.09; 95% confidence interval, CI: 1.02-1.16) and liver cancer (HR: 1.49; 95% CI: 1.11-2.01). Large early-adulthood body size was associated with liver cancer (HR: 1.85; 95% CI: 1.35-2.52). Compared with normal weight during all stages, overweight or obesity during adolescence only or early adulthood only were associated with stomach cancer, esophageal squamous cell carcinoma, and liver cancer. Lower levels of adolescent occupational PA were associated with colon cancer (HR: 1.39; 95% CI: 1.10-1.75), while lower levels at cohort baseline were positively associated with colon cancer and inversely associated with rectal cancer. Our findings suggest that timing of obesity during the life course might differently affect risk of gastrointestinal cancers, while occupational PA was found to be associated with colon cancer only., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

Background: The global burden of non-alcoholic fatty liver disease (NAFLD) has significantly risen over the past decade. Dietary intake strongly influences its development and should be a component of any prevention and treatment plan strategy. Dietary pattern analysis enables the investigation of the overall diet and permits the consideration of interactions and cumulative effects of dietary components. The current study aimed to systematically review observational studies and intervention trials to determine the associations between various dietary patterns and NAFLD., Methods: The protocol was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase, and the Cochrane Library. We included studies that reported a priori dietary pattern (i.e., diet quality scores) or a posteriori method, which identified existing eating patterns (i.e., principal component analysis) in adult participants. Two investigators conducted independent screening, extraction, and quality assessment using the Newcastle‒Ottawa or Jadad scale. A third reviewer resolved conflicts., Results: We identified 27 relevant observational and 16 interventional studies from 16 countries. A Mediterranean or DASH diet might prevent and improve NAFLD, whereas dietary patterns such as Western dietary patterns characterized by high consumption of sweets and animal foods such as red meat and fast food are positively associated with NAFLD. A low-carbohydrate diet effectively prevents and treats NAFLD; however, we need more research on the effects of a low-fat diet and the type of fats., Conclusion: Healthy dietary patterns, mainly plant-based or adjusted macronutrient distributions, such as the adoption of a low-carbohydrate diet, are linked to a reduced risk of NAFLD and could halt its progression. We proposed recommendations for future studies to fill the gap in knowledge regarding the management of NAFLD via dietary modifications., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

A male predominance was observed in esophageal and gastric cancers, though present limited data has revealed variations by age. We aim to investigate the global age-specific sex differences in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Data on esophageal and gastric cancers incidence by diagnosis year, sex, histology, subsite and age group were extracted from 171 registries in 54 countries included in the last two volumes (X and XI, 2003-2012) of Cancer Incidence in Five Continents, which contributing to over 80% of the global burdens of these cancers. Age-standardized incidence rates (ASIRs) and male-to-female ASIRs ratios were estimated for esophageal and gastric cancers, by histological subtype and subsite, globally and by country. We consistently observed a male predominance in esophageal and gastric cancers across the world from 2003 to 2012, with male-to-female ASIRs ratios of 6.7:1 for EAC, 3.3:1 for ESCC, 4.0:1 for GCC and 2.1:1 for GNCC. The sex differences were consistent across time periods but varied significantly by age across the life span. Across the four cancer types, the male-to-female incidence rate ratios increased from young ages, approaching a peak at ages 60-64, but sharply declined thereafter. Similar "low-high-low" trends of age-specific sex ratio were observed in other digestive cancers including liver, pancreas, colon and rectum with peak ages ranging from 50 to 65. Age-dependent risk factors warrant further investigation to aid our understanding of the underlying etiologies of esophageal and gastric cancers by histological subtype and subsite., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Environmental exposures account for a growing proportion of global mortality. Large cohort studies are needed to characterize the independent impact of environmental exposures on mortality in low-income settings., Methods: We collected data on individual and environmental risk factors for a multiethnic cohort of 50,045 individuals in a low-income region in Iran. Environmental risk factors included: ambient fine particular matter air pollution; household fuel use and ventilation; proximity to traffic; distance to percutaneous coronary intervention (PCI) center; socioeconomic environment; population density; local land use; and nighttime light exposure. We developed a spatial survival model to estimate the independent associations between these environmental exposures and all-cause and cardiovascular mortality., Findings: Several environmental factors demonstrated associations with mortality after adjusting for individual risk factors. Ambient fine particulate matter air pollution predicted all-cause mortality (per μg/m3, HR 1.20, 95% CI 1.07, 1.36) and cardiovascular mortality (HR 1.17, 95% CI 0.98, 1.39). Biomass fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.23, 95% CI 0.99, 1.53) and cardiovascular mortality (HR 1.36, 95% CI 0.99, 1.87). Kerosene fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.09, 95% CI 0.97, 1.23) and cardiovascular mortality (HR 1.19, 95% CI 1.01, 1.41). Distance to PCI center predicted all-cause mortality (per 10km, HR 1.01, 95% CI 1.004, 1.022) and cardiovascular mortality (HR 1.02, 95% CI 1.004, 1.031). Additionally, proximity to traffic predicted all-cause mortality (HR 1.13, 95% CI 1.01, 1.27). In a separate validation cohort, the multivariable model effectively predicted both all-cause mortality (AUC 0.76) and cardiovascular mortality (AUC 0.81). Population attributable fractions demonstrated a high mortality burden attributable to environmental exposures., Interpretation: Several environmental factors predicted cardiovascular and all-cause mortality, independent of each other and of individual risk factors. Mortality attributable to environmental factors represents a critical opportunity for targeted policies and programs., Competing Interests: The authors have declared that no competing interests exist.

Objective: To prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers., Design and Setting: A nested case-control study within two prospective cohort studies, the Shanghai Women's Health Study (n=74 941) and the Shanghai Men's Health Study (n=61 480)., Participants: Lifetime never-smokers who had no cancer at baseline. Cases were subjects who were diagnosed with incident lung cancer (n=114) and were matched 1:1 with controls on sex, age (≤2 years), date (≤30 days) and time (morning/afternoon) of sample collection, antibiotic use during the week before sample collection (yes/no) and menopausal status (for women)., Main Outcomes and Measures: Metagenomic shotgun sequencing was used to measure the community structure and abundance of the oral microbiome in pre-diagnostic oral rinse samples of each case and control. Multivariable logistic regression models were used to estimate the association of lung cancer risk with alpha diversity metrics and relative abundance of taxa. The Microbiome Regression-Based Kernel Association Test (MiRKAT) evaluated the association between risk and the microbiome beta diversity., Results: Subjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: p trend =0.05; Simpson: p trend =0.04; Observed Species: p trend =0.64). No case-control differences were apparent for beta diversity (p MiRKAT =0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (OR low 1.00 (reference), OR medium 0.61 (95% CI 0.32 to 1.18), OR high 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (OR low 1.00 (reference), OR medium 0.66 (95% CI 0.35 to 1.25), OR high 0.31 (95% CI 0.15 to 0.64)) was associated with a decreased risk of lung cancer, while a greater abundance of the Bacilli class (OR low 1.00 (reference), OR medium 1.49 (95% CI 0.73 to 3.08), OR high 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (OR low 1.00 (reference), OR medium 2.15 (95% CI 1.03 to 4.47), OR high 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer., Conclusions: Our prospective study of never-smokers suggests that lower alpha diversity was associated with a greater risk of lung cancer and the abundance of certain specific taxa was associated with altered risk, providing further insight into the aetiology of lung cancer in the absence of active tobacco smoking., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: This study aimed to evaluate effects of endoscopic screening method in different starting age groups and further confirm the optimum starting age for esophageal squamous cell cancer (ESCC) screening., Methods: This study received institutional review board approval, and 6825 residents aged 40 to 69 years in high prevalence communities were assigned to the screening group or the control (non-screening) group from Hebei, China. Cumulative mortalities during the 14-year period, relative risk for participants who underwent screening, and numbers needed to invite for screening to save one life were compared between the screening group and the control group of different starting age groups at 14-year follow-up., Results: The 14-year risks of ESCC mortality were one in 55, one in 17, and one in 9 for a person screened in the starting age group of 40, 50, and 60 years old. The cumulative mortalities of ESCC in screening groups were significantly lower than control groups in starting age groups of 40 years (1.42% vs 2.38%, P = 0.033) and 50 years (4.18% vs 7.13%, P = 0.005). Relative risks for participants who underwent screening were 0.60 and 0.59 for the starting age groups of 40 and 50 years. Numbers needed to invite for screening to save one life were 104 and 34 for participants in 40 years old group and 50 years old group, respectively., Conclusions: In conclusion, people in high prevalence area of ESCC should have endoscopy screening once at their 50 years. Forty years will be preferably defined as the starting age for screening in areas with sufficient health resources., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Gut microbiota from individuals in rural, non-industrialized societies differ from those in individuals from industrialized societies. Here, we use 16S rRNA sequencing to survey the gut bacteria of seven non-industrialized populations from Tanzania and Botswana. These include populations practicing traditional hunter-gatherer, pastoralist, and agropastoralist subsistence lifestyles and a comparative urban cohort from the greater Philadelphia region., Results: We find that bacterial diversity per individual and within-population phylogenetic dissimilarity differs between Botswanan and Tanzanian populations, with Tanzania generally having higher diversity per individual and lower dissimilarity between individuals. Among subsistence groups, the gut bacteria of hunter-gatherers are phylogenetically distinct from both agropastoralists and pastoralists, but that of agropastoralists and pastoralists were not significantly different from each other. Nearly half of the Bantu-speaking agropastoralists from Botswana have gut bacteria that are very similar to the Philadelphian cohort. Based on imputed metagenomic content, US samples have a relative enrichment of genes found in pathways for degradation of several common industrial pollutants. Within two African populations, we find evidence that bacterial composition correlates with the genetic relatedness between individuals., Conclusions: Across the cohort, similarity in bacterial presence/absence compositions between people increases with both geographic proximity and genetic relatedness, while abundance weighted bacterial composition varies more significantly with geographic proximity than with genetic relatedness.

Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5 , MFSD12 , DDB1 , TMEM138 , OCA2 , and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in South Asian and Australo-Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of ultraviolet response genes under selection in Eurasians., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in most Eastern and Southern African countries, but its etiology has been understudied to date. To inform its research agenda, we undertook a review to identify, of the ESCC risk factors which have been established or strongly suggested worldwide, those with a high prevalence or high exposure levels in any ESCC-affected African setting and the sources thereof. We found that for almost all ESCC risk factors known to date, including tobacco, alcohol, hot beverage consumption, nitrosamines and both inhaled and ingested PAHs, there is evidence of population groups with raised exposures, the sources of which vary greatly between cultures across the ESCC corridor. Research encompassing these risk factors is warranted and is likely to identify primary prevention strategies., (© 2016 IARC/WHO.)