High-risk Area Of China Research Articles

Analysis of risky sexual behaviors among male college students who were sexually active in Sichuan, China: a cross-sectional survey

BackgroundMales have accounted for a significant share of new HIV infections among young people in the recent years. This study aimed to identify the factors associated with risky sexual behaviors, including early sexual debut, multiple sexual partnership and condomless sex, among sexually active male college students and provide implications for tailored health interventions.MethodsThe cross-sectional study was conducted from December 2020 to December 2021 in 16 colleges that were located in Sichuan Province, one of the high-risk areas in China. Overall 1640 male college students who reported sexually experienced were analyzed in this study. Multivariable logistic regression analysis was applied to determine factors associated with early sexual debut, multiple sexual partnership and condomless sex.ResultsThe average age of included male students was 19.95 ± 1.56. Of them, 27.74% initiated sexual behavior early, 48.60% reported multiple sexual partnership, and 16.52% did not use condoms at the latest sexual intercourse. Students who were younger (age ≤ 19, AOR = 7.60, 95%CI: 4.84–11.93; age20-21, AOR = 3.26, 95%CI: 2.04–5.21) and self-identified as sexual minorities (AOR = 2.38, 95%CI: 1.69–3.36) were more likely to have early sexual debut. The odds of having multiple sexual partners were higher among those who were ethnic minorities (AOR = 1.79, 95%CI: 1.33–2.41) and accepted extramarital sex (AOR = 1.33, 95%CI: 1.03–1.71). The likelihood of engaging in condomless sex at the latest sexual intercourse was lower among those who had sufficient knowledgeable about HIV (AOR = 0.63, 95%CI: 0.44–0.89), were very confident in condom use efficacy (AOR = 0.26, 95%CI: 0.16–0.43) and confident (AOR = 0.48, 95%CI: 0.34–0.69). Early sexual debut was positively associated with multiple sexual partnership (AOR = 3.64, 95%CI: 2.82–4.71) and condomless sex at the latest intercourse (AOR = 1.53, 95%CI: 1.07–2.20), respectively.ConclusionEarly sexual debut, multiple sexual partnership and condomless sex were of considerable concern among male college students. Comprehensive sex education curricula were advised by developing customized information on HIV prevention, sexuality and empowering students with assertiveness and negotiation skills with regard to condom use during and before college.

Plant-based dietary patterns and risk of esophageal cancer: A prospective cohort study spanning 17 years.

Plant-based diets have multiple health benefits for cancers; however, little is known about the association between plant-based dietary patterns and esophageal cancer (EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC. We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) of EC across 3 plant-based diet indices and further stratified the analysis by subgroups. The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365 person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50 (95% CI, 0.32-0.77) for hPDI. In addition, the HR per 10-point increase in the hPDI score was 0.42 (95% CI, 0.27-0.66) for ECs. Conversely, uPDI was positively associated with the risk of EC, and the HR was 1.80 (95% CI, 1.16-2.82). The HR per 10-point increase in the uPDI score was 1.90 (95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses. A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

Performance of Prediction Models for Esophageal Squamous Cell Carcinoma in General Population: A Systematic Review and External Validation Study.

Prediction models for esophageal squamous cell carcinoma (ESCC) need to be proven effective in the target population before they can be applied to population-based endoscopic screening to improve cost-effectiveness. We have systematically reviewed ESCC prediction models applicable to the general population and performed external validation and head-to-head comparisons in a large multicenter prospective cohort including 5 high-risk areas of China (Fei Cheng, Lin Zhou, Ci Xian, Yang Zhong, and Yan Ting). Models were identified through a systematic review and validated in a large population-based multicenter prospective cohort that included 89,753 participants aged 40-69 years who underwent their first endoscopic examination between April 2017 and March 2021 and were followed up until December 31, 2022. Model performance in external validation was estimated based on discrimination and calibration. Discrimination was assessed by C-statistic (concordance statistic), and calibration was assessed by calibration plot and Hosmer-Lemeshow test. The systematic review identified 15 prediction models that predicted severe dysplasia and above lesion (SDA) or ESCC in the general population, of which 11 models (4 SDA and 7 ESCC) were externally validated. The C-statistics ranged from 0.67 (95% confidence interval 0.66-0.69) to 0.70 (0.68-0.71) of the SDA models, and the highest was achieved by Liu et al (2020) and Liu et al (2022). The C-statistics ranged from 0.51 (0.48-0.54) to 0.74 (0.71-0.77), and Han et al (2023) had the best discrimination of the ESCC models. Most models were well calibrated after recalibration because the calibration plots coincided with the x = y line. Several prediction models showed moderate performance in external validation, and the prediction models may be useful in screening for ESCC. Further research is needed on model optimization, generalization, implementation, and health economic evaluation.

Modeling the forest fire risk by incorporating a new human activity factor from nighttime light data

Fire was a serious natural disturbance to forest ecosystems. In this study, a national-scale forest fire risk model (RF_NTL) was proposed in mainland China by incorporating a new human activity factor (NTL) from nighttime light data. For objective verification of model’s performance, the logistic regression model (LR) and random forest model (RF) were also built in this paper. Results showed that the RF_NTL model fitted with an AUC value up to 0.95, which was superior to the conventional LR model and RF model. The RF_NTL model also had good generalization ability and stability on annual and monthly scales, helping to accurately forecast forest fire risk. Moreover, the spatial distribution of forest fire risk based on RF_NTL model was detailed and reasonable on a national scale. Forest fire high-risk areas in China were mainly concentrated in the northeast and southwest regions. This study could provide references for future relevant research.

Overview of Risk Factors for Esophageal Squamous Cell Carcinoma in China.

(1) Background: China has the highest esophageal squamous cell carcinoma (ESCC) incidence areas in the world, with some areas of incidence over 100 per 100,000. Despite extensive public health efforts, its etiology is still poorly understood. This study aims to review and summarize past research into potential etiologic factors for ESCC in China. (2) Methods: Relevant observational and intervention studies were systematically extracted from four databases using key terms, reviewed using Rayyan software, and summarized into Excel tables. (3) Results: Among the 207 studies included in this review, 129 studies were focused on genetic etiologic factors, followed by 22 studies focused on dietary-related factors, 19 studies focused on HPV-related factors, and 37 studies focused on other factors. (4) Conclusions: ESCC in China involves a variety of factors including genetic variations, gene-environment interactions, dietary factors like alcohol, tobacco use, pickled vegetables, and salted meat, dietary behavior such as hot food/drink consumption, infections like HPV, poor oral health, gastric atrophy, and socioeconomic factors. Public health measures should prioritize genetic screening for relevant polymorphisms, conduct comprehensive investigations into environmental, dietary, and HPV influences, enhance oral health education, and consider socioeconomic factors overall as integral strategies to reduce ESCC in high-risk areas of China.

Predicting Risk Areas of Classical Scrapie in China Based on Environmental Suitability

Classical scrapie is a transmissible spongiform encephalopathy that attacks the central nervous system of sheep and goats. Since its discovery in the 18th century, the disease has caused enormous economic losses and public health impacts in continental Europe. In the late 20th century, classical scrapie began to spread to places, such as Asia and the Americas, becoming a disease of global concern. In this study, based on prion occurrence records and high-resolution environmental layers, a risk assessment of classical scrapie in China was performed using a maximum entropy model. The model achieved an area under the curve value of 0.906 (95% confidence interval, 0.0883–0.0929). Sheep distribution density, road density, goat distribution density, minimum temperature of the coldest month, port density, and precipitation of the driest quarter were identified as important factors affecting the occurrence of classical scrapie. The risk map showed that potential high-risk areas in China were mainly located in Northeast China, North China, and Northwest China. This study can provide a valuable reference for the prevention of classical scrapie in China. According to the environmental variables and risk areas of classical scrapie, implementing monitoring and early warning measures in these areas is recommended to reduce the possibility of classical scrapie occurrence and transmission.

Associations between cancer family history and esophageal cancer and precancerous lesions in high-risk areas of China.

Background:Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations.Methods:This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL.Results:Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36–1.62), 1.52-fold (95% CI: 1.38–1.67), or 1.66-fold (95% CI: 1.50–1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47–1.84) or 1.93-fold (95% CI: 1.46–2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30–12.65), 2.11-fold (95% CI: 1.37–3.25), and 1.91-fold (95% CI: 1.44–2.54) higher risks of ECPL, respectively.Conclusions:Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation.Trial registration:ChiCTR-EOC-17010553.

The epidemiological characteristics of dengue in high-risk areas of China, 2013-2016.

IntroductionDengue has become a more serious human health concern in China, with increased incidence and expanded outbreak regions. The knowledge of the cross-sectional and longitudinal epidemiological characteristics and the evolutionary dynamics of dengue in high-risk areas of China is limited.MethodsRecords of dengue cases from 2013 to 2016 were obtained from the China Notifiable Disease Surveillance System. Full envelope gene sequences of dengue viruses detected from the high-risk areas of China were collected. Maximum Likelihood tree and haplotype network analyses were conducted to explore the phylogenetic relationship of viruses from high-risk areas of China.ResultsA total of 56,520 cases was reported in China from 2013 to 2016. During this time, Yunnan, Guangdong and Fujian provinces were the high-risk areas. Imported cases occurred almost year-round, and were mainly introduced from Southeast Asia. The first indigenous case usually occurred in June to August, and the last one occurred before December in Yunnan and Fujian provinces but in December in Guangdong Province. Seven genotypes of DENV 1–3 were detected in the high-risk areas, with DENV 1-I the main genotype and DENV 2-Cosmopolitan the secondary one. The Maximum Likelihood trees show that almost all the indigenous viruses separated into different clusters. DENV 1-I viruses were found to be clustered in Guangdong Province, but not in Fujian and Yunnan, from 2013 to 2015. The ancestors of the Guangdong viruses in the cluster in 2013 and 2014 were most closely related to strains from Thailand or Singapore, and the Guangdong virus in 2015 was most closely related to the Guangdong virus of 2014. Based on closest phylogenetic relationships, viruses from Myanmar possibly initiated further indigenous cases in Yunnan, those from Indonesia in Fujian, while viruses from Thailand, Malaysia, Singapore and Indonesia were predominant in Guangdong Province.ConclusionsDengue is still an imported disease in China, although some genotypes continued to circulate in successive years. Viral phylogenies based on the envelope gene suggested periodic introductions of dengue strains into China, primarily from Southeast Asia, with occasional sustained, multi-year transmission in some regions of China.

Cost-effectiveness of risk-stratified endoscopic screening for esophageal cancer in high-risk areas of China: a modeling study

Risk-stratified endoscopic screening (RSES) has been suggested to improve screening efficiency. We aimed to assess the cost-effectiveness of RSES and identify the optimal risk-score thresholds for once in a lifetime esophageal cancer (EC) screening in high-risk areas of China. From a healthcare system perspective, a Markov model was constructed to compare the cost-effectiveness of 13 RSES strategies (under different score thresholds for EC risk), universal endoscopic screening strategy, and no screening. Six cohorts of 100,000 participants with different screening ages (40-65 years) were followed up to age 77 years. The incremental cost-effectiveness ratio (ICER), that is, incremental costs per quality-adjusted life-year (QALY) gained, was the primary outcome. Compared with no screening, as the score threshold was lowered, additionally gained QALYs increased, with 49 to 172 QALYs and 329 to 1147 QALYs gained from screening performed at 40 and 65 years, respectively. RSES in all age scenarios had ICERs less than the gross domestic product (GDP) per capita, and 11 RSES strategies with score thresholds of 3 to 13 had lower ICERs than universal endoscopic screening. At a willingness-to-pay threshold of the GDP per capita (U.S.$10,276/QALY), RSES at score thresholds of 8 or 9 and universal endoscopic screening were the most cost-effective strategies at ages<55 and≥55 years, respectively. RSES is cost-effective, and score thresholds of 8 or 9 should be considered for screening ages<55 years. For individuals aged≥55 years, universal endoscopic screening is the optimal strategy.

Estimated Cost-effectiveness of Endoscopic Screening for Upper Gastrointestinal Tract Cancer in High-Risk Areas in China

Upper gastrointestinal tract cancer, including esophageal and gastric cancers, in China accounts for 50% of the global burden. Endoscopic screening may be associated with a decreased incidence of and mortality from upper gastrointestinal tract cancer. To evaluate the cost-effectiveness of endoscopic screening for esophageal and gastric cancers among people aged 40 to 69 years in areas of China where the risk of these cancers is high. For this economic evaluation, a Markov model was constructed for initial screening at different ages from a health care system perspective, and 5 endoscopic screening strategies with different frequencies (once per lifetime and every 10 years, 5 years, 3 years, and 2 years) were evaluated. The study was conducted between January 1, 2019, and October 31, 2020. Model parameters were estimated based on this project, government documents, and published literature. For each initial screening age (40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a closed cohort of 100 000 participants was assumed to enter the model and follow the alternative strategies. Cost-effectiveness was measured by calculating the incremental cost-effectiveness ratio (ICER), and the willingness-to-pay threshold was assumed to be 3 times the per capita gross domestic product in China (US $10 276). Univariate and probabilistic sensitivity analyses were conducted to assess the robustness of model findings. The study included a hypothetical cohort of 100 000 individuals aged 40 to 69 years. All 5 screening strategies were associated with improved effectiveness by 1087 to 10 362 quality-adjusted life-years (QALYs) and increased costs by US $3 299 000 to $22 826 000 compared with no screening over a lifetime, leading to ICERs of US $1343 to $3035 per QALY. Screening at a higher frequency was associated with an increase in QALYs and costs; ICERs for higher frequency screening compared with the next-lower frequency screening were between US $1087 and $4511 per QALY. Screening every 2 years would be the most cost-effective strategy, with probabilities of 90% to 98% at 3 times the per capita gross domestic product of China. The model was the most sensitive to utility scores of esophageal cancer- or gastric cancer-related health states and compliance with screening. The findings suggest that combined endoscopic screening for esophageal and gastric cancers may be cost-effective in areas of China where the risk of these cancers is high; screening every 2 years would be the optimal strategy. These data may be useful for development of policies targeting the prevention and control of upper gastrointestinal tract cancer in China.

Improved esophageal squamous cell carcinoma screening effectiveness by risk-stratified endoscopic screening: evidence from high-risk areas in China.

BackgroundRisk‐stratified endoscopic screening (RSES), which offers endoscopy to those with a high risk of esophageal cancer, has the potential to increase effectiveness and reduce endoscopic demands compared with the universal screening strategy (i.e., endoscopic screening for all targets without risk prediction). Evidence of RSES in high‐risk areas of China is limited. This study aimed to estimate whether RSES based on a 22‐score esophageal squamous cell carcinoma (ESCC) risk prediction model could optimize the universal endoscopic screening strategy for ESCC screening in high‐risk areas of China.MethodsEight epidemiological variables in the ESCC risk prediction model were collected retrospectively from 26,618 individuals aged 40‐69 from three high‐risk areas of China who underwent endoscopic screening between May 2015 and July 2017. The model's performance was estimated using the area under the curve (AUC). Participants were categorized into a high‐risk group and a low‐risk group with a cutoff score having sensitivities of both ESCC and severe dysplasia and above (SDA) at more than 90.0%.ResultsThe ESCC risk prediction model had an AUC of 0.80 (95% confidence interval: 0.75–0.84) in this external population. We found that a score of 8 (ranging from 0 to 22) had a sensitivity of 94.2% for ESCC and 92.5% for SDA. The RSES strategy using this threshold score would allow 50.6% of endoscopies to be avoided and save approximately US$ 0.59 million compared to universal endoscopic screening among 26,618 participants. In addition, a higher prevalence of SDA (1.7% vs. 0.9%), a lower number need to screen (60 vs. 111), and a lower average cost per detected SDA (US$ 3.22 thousand vs. US$ 5.45 thousand) could have been obtained by the RSES strategy.ConclusionsThe RSES strategy based on individual risk has the potential to optimize the universal endoscopic screening strategy in ESCC high‐risk areas of China.

Cost-Effectiveness of Risk-Stratified Endoscopic Screening for Esophageal Cancer in High-Risk Areas of China: A Modeling Study

Background: Risk-stratified endoscopic screening (RSES), which provides endoscopies to individuals at high risk for esophageal cancer (EC), has been suggested to improve screening efficiency. We aimed to assess the cost-effectiveness of RSES and identify the optimal thresholds for EC screening in high-risk areas of China. Methods: From a healthcare system perspective, a Markov model was constructed to compare the cost-effectiveness of 13 RSES strategies (under different threshold scores of EC risk), universal endoscopic screening strategy, and no screening. Six cohorts of 100 000 women and men with different start ages (40, 45, 50, 55, 60 and 65 years) with follow-up to age 77 years. The incremental cost-effectiveness ratio (ICER), i.e., the incremental cost per quality-adjusted life-years (QALYs) gained, was the primary outcome. Univariate and probabilistic sensitivity analyses were conducted. Findings: Compared with no screening, as the score threshold of the RSES was lowered, additionally gained QALYs increased, with 49−172 QALYs and 329−1258 QALYs gained from 40 years to 65 years. RSES in all age scenarios had ICERs less than 1×GDP per capita (US$10 276/QALY), and 11 RSES strategies with threshold scores of 3–13 had lower ICERs than universal endoscopic screening. Compared to universal endoscopic screening, which had the largest health gains than no screening, RSES with threshold scores of 8, 9, and 10 decreased cost by US$ 0‧35 0–47 million and reduced endoscopies by 7692–9943 with a slight decrease in QALYs. At a willingness-to-pay threshold of US$10 276/QALY, RSES (with threshold scores of 8 and 9) and universal endoscopic screening had a 43‧8–51‧7% and a 49‧6–67‧5% probability of being the most cost-effective at the age of <55 years and ≥ 55 years. Interpretation: RSES is cost-effective in high-risk areas of China. RSES with threshold scores of 8 would be recommended if EC screening was considered for residents aged 40–69 in high-risk areas of China. Funding Information: This work was supported by the Key Technologies Research and Development Program in China (2018YFC1313100), the National High-tech Research and Development Program (grant number: 201502001), the Beijing Science and Technology Planning Project [grant number: J200017], and the Sanming Project of Medicine in Shenzhen (grant number: SZSM201911015). Declaration of Interests: We declare that all authors have no conflicts of interest or financial interests to disclose.

A nomogram for screening esophageal squamous cell carcinoma based on environmental risk factors in a high-incidence area of China: a population-based case-control study

BackgroundSelection of high-risk subjects for endoscopic screening of esophageal squamous cell carcinoma (ESCC) lacks individual predictive tools based on environmental risk factors.MethodsWe performed a large population-based case-control study of 1418 ESCC cases and 1992 controls in a high-risk area of China. Information on potential risk factors was collected via face-to-face interview using an electronic structured questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models, and predictive nomograms were established accordingly. A weighted analysis was further conducted to introduce age into predictive nomograms due to frequency matching study design.ResultsMost cases were usually exposed to 4 to 6 risk factors, but most controls were usually exposed to 3 to 5 risk factors. The AUCs of male and female predictive nomograms were 0.75 (95%CI: 0.72, 0.77) and 0.76 (95%CI: 0.73, 0.79), respectively. The weighted analysis adding age in the predictive model improved the AUC in both men and women (0.81 (95%CI: 0.79, 0.84) and 0.88 (95%CI: 0.85, 0.90), respectively).ConclusionsAn easy-to-use preclinical predictive tool is provided to select candidate population with high ESCC risk for endoscopic screening. Its usefulness needs to be further evaluated in future screening practice.

Genetic Polymorphisms in DNA Repair Gene APE1/Ref-1 and the Risk of Neural Tube Defects in a High-Risk Area of China.

Apurinic/apyrimidinic endonuclease 1/redox-factor 1 (APE1/Ref-1) gene encodes a multifunctional protein involved in the DNA base excision repair (BER) pathway, which initiates repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone. APE1/Ref-1 polymorphisms are related to the occurrence of neural tube defects (NTDs), but the association between APE1/Ref-1 polymorphisms and NTDs is not reported in Chinese Han population. The aim of the present study was to evaluate the association of APE1/Ref-1 polymorphism and the risk of NTD occurrence for Han population in a high-risk area of China. APE1/Ref-1 genotypes were determined by iPLEX Gold SNP genotyping. AP sites and folate level of brain tissues were measured. The results showed that three polymorphisms (rs3136817, rs77794916, and rs1760944) of APE1/Ref-1 were statistically associated with NTD subtypes. Allele C of rs3136817, allele T of rs77794916, and allele G of rs1760944 were associated with an increased risk for encephalocele (OR = 2.52, 95% CI [1.25-5.07], P < 0.01; OR = 1.80, 95% CI [1.04-3.12], P = 0.04; and OR = 1.96, 95% CI [1.12-3.45], P = 0.02), compared with those harboring the alleles T, C, and T, respectively. The folate level in NTDs was lower than that in controls. DNA AP sites in the encephalocele were significantly higher than the control (P < 0.01). The three polymorphisms of APE1/Ref-1 were significantly related to NTD occurrence, which indicated that APE1/Ref-1 might be a potential genetic risk factor for encephalocele in a high-risk area of NTDs in China.

Dietary flavonoid intake and risk of esophageal squamous cell carcinoma: A population-based case-control study

ObjectivesThe aim of this population-based case-control study was to investigate the association between dietary consumption of the total flavonoids, subclasses, and specific flavonoids and the risk of esophageal squamous cell carcinoma (ESCC) among adults in a high-risk area of China. MethodsWe recruited 820 ESCC participants and 863 control participants from Yanting County. Dietary flavonoids were assessed using a validated 76-item food frequency questionnaire. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression after considering potential confounders. ResultsComparing the highest and lowest intake quartiles, we observed a negative association of ESCC risk with consumption of isoflavones (OR = 0.34, 95% CI = 0.23–0.50, P for trend < 0.001), daidzein (OR = 0.31, 95% CI = 0.21–0.45, P for trend < 0.001), genistein (OR = 0.34, 95% CI = 0.23–0.50, P for trend < 0.001), and glycitein (OR = 0.32, 95% CI = 0.22–0.48, P for trend < 0.001) after adjustment for potential confounders. A more pronounced negative association was observed when comparing the third quartile, rather than the fourth, with the lowest quartile for consumption of anthocyanidins (OR = 0.58, 95% CI = 0.42–0.80, P for trend = 0.004), delphinidin (OR = 0.57, 95% CI = 0.41–0.78, P for trend = 0.004), and cyanidin (OR = 0.48, 95% CI = 0.35–0.66, P for trend = 0.003) after considering potential confounders. Consumption of total flavonoids, flavones, flavonols, and six other specific flavonoids (quercetin, myricetin, kaempferol, luteolin, apigenin, and peonidin) was not associated with ESCC risk. ConclusionsThe results suggest that increased dietary intake of isoflavones and moderate consumption of anthocyanidins were associated with a decreased risk of ESCC. Future nutritional guidelines may emphasize foods or supplements rich in specific isoflavones and anthocyanidins for ESCC chemoprevention.

Targeted proteomics-derived biomarker profile develops a multi-protein classifier in liquid biopsies for early detection of esophageal squamous cell carcinoma from a population-based case-control study

BackgroundEarly diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for the early detection of ESCC.MethodsWe selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay.ResultsWe found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early-stage ESCC from healthy controls, which were validated by the significant dose-response relationships with ESCC pathological progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14 (kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in the final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899 ~ 0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation.ConclusionsOur study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC, especially with the establishment of a three-level hierarchical screening strategy for ESCC control.

Estimating Individualized Absolute Risk for Esophageal Squamous Cell Carcinoma: A Population-Based Study in High-Risk Areas of China.

BackgroundEsophageal squamous cell carcinoma (ESCC) has a high incidence rate and poor prognosis. In this study, we aimed to develop a predictive model to estimate the individualized 5-year absolute risk for ESCC in Chinese populations living in the high-risk areas of China.MethodsWe developed a risk-predicting model based on the epidemiologic data from a population-based case-control study including 244 newly diagnosed ESCC patients and 1,220 healthy controls. Initially, we included easy-to-obtain risk factors to construct the model using the multivariable logistic regression analysis. The area under the ROC curves (AUC) with cross-validation methods was used to evaluate the performance of the model. Combined with local age- and sex-specific ESCC incidence and mortality rates, the model was then used to estimate the absolute risk of developing ESCC within 5 years.ResultsA relative risk model was established that included eight factors: age, sex, tobacco smoking, alcohol drinking, education, and dietary habits (intake of hot food, intake of pickled/salted food, and intake of fresh fruit). The relative risk model had good discrimination [AUC, 0.785; 95% confidence interval (CI), 0.749–0.821]. The estimated 5-year absolute risk of ESCC for individuals varied widely, from 0.0003% to 19.72% in the studied population, depending on the exposure to risk factors.ConclusionsOur model based on readily identifiable risk factors showed good discriminative accuracy and strong robustness. And it could be applied to identify individuals with a higher risk of developing ESCC in the Chinese population, who might benefit from further targeted screening to prevent esophageal cancer.

Comprehensive dietary and internal exposure assessment of deoxynivalenol contamination in a high-risk area in China using duplicate diet studies and urinary biomarkers

This study assessed the exposure of 199 Chinese population samples from the Anhui Province, China, to deoxynivalenol (DON) based on their dietary intake and urinary biomarkers. This is the first study to compare between both procedures of DON exposure detection (diet study and human bio-monitoring approach) within the same population. Food and urine samples were collected from 199 healthy participants. The highest concentrations of DON and its derivatives were detected in wheat-based products. Both DON and its metabolite, DOM-1, were found in the urine samples. Total (free + conjugated) DON was detected in 99% of the samples, with a mean concentration at 109.21 ng mL−1. The mean estimated dietary intake (EDI) level calculated from food consumption and contamination data was obtained as 2.54 ± 1.63 μg kg−1 bw d−1, while the mean probable daily intake (PDI) based on urinary biomarkers was estimated to be 3.96 ± 4.20 μg kg−1 bw d−1. A significant correlation was evidenced between EDI and PDI, both exceeding the provisional maximum tolerable daily intake. Elevated contaminant levels were observed in the adolescent group compared to children, adults, and elders, thereby indicating a potential health risk in them. The excretion rate of adolescents was approximately 2.5 times that of adult participants, possibly indicative of higher metabolic activity, which needs further in-depth investigation.

Trefoil factor 1 and gastrokine 2 inhibit Helicobacter pylori-induced proliferation and inflammation in gastric cardia and distal carcinogenesis.

Helicobacter pylori (H. pylori) infection has been associated with non-cardia adenocarcinoma in the stomach, while its role in gastric cardia adenocarcinoma (GCA) remains controversial. In addition, the association between H. pylori and the protective factors trefoil factor 1 (TFF1) and gastrokine 2 (GKN2) in gastroesophageal adenocarcinomas has not been fully investigated. Therefore, the mRNA and protein expression levels of TFF1 and GKN2 in GCA and distal gastric adenocarcinoma (DGA) were analyzed using quantitative PCR (qPCR) and immunohistochemistry, and the association with H. pylori infection was investigated. In addition, the effects of TFF1 and GKN2 overexpression on H. pylori-induced cells were investigated using western blot and reverse transcription-qPCR analysis. The comparative analysis of 16S rRNA-positive mRNA expression between GCA and DGA showed no statistically significant difference. However, the rate of the H. pylori vacuolating toxin A (VacA) genotype was significantly higher in GCA (49.2%) compared with that in DGA (26.9%; P<0.05). H. pylori infection downregulated the mRNA and protein expression levels of TFF1 and GKN2 in gastric tumor tissues, and the mRNA expression level of TFF1 and GKN2 was also markedly decreased in vitro. Furthermore, the cell proliferation varied in H. pylori total protein treatment group with the different doses. Notably, treatment with 20 µg/ml H. pylori total protein for 24 h resulted in the highest cellular proliferation rate. In addition, TFF1 and GKN2 overexpression inversely inhibited H. pylori-induced cell proliferation and upregulated NF-κB, tumor necrosis factor-α, IL-1β, IL-2, IL-4 and IL-6. The results of the present study indicate that H. pylori, particularly the VacA+ strain, plays an important role in GCA pathogenesis in high-risk areas of China, while TFF1/GKN2 inhibits H. pylori-induced cell proliferation and inflammation in GCA and DGA.

164 EFFECTIVENESS OF ONE-TIME ENDOSCOPIC SCREENING PROGRAM IN PREVENTION OF ESOPHAGEAL CANCER IN CHINA: A MULTI-CENTER POPULATION-BASED COHORT STUDY

Abstract Esophageal cancer is one of the most common cancers worldwide and half of all new cases occurred in China. Population-based endoscopic screening has been carried out in some high-risk areas in China since 2005, but previous evidence was based predominately on small-sample, single-center studies. We undertook a population-based, multi-center cohort study to estimate the effectiveness of endoscopic screening program in reducing the incidence and mortality of esophageal in high risks areas in China. Methods This study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40–69 yeas were identified as target subjects. We defined those who were invited and undertook endoscopic screening as the screened group, and those who refused screening as the non-screened group. The target subjects who were not invited to screening was assigned to the control group. The effectiveness of endoscopic screening and screening program were evaluated by comparing the reductions in the incidence and mortality from esophageal cancer in those screened or those invited to screening with reductions in the control group, respectively. Results Our cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, esophageal cancer incidence and mortality were reduced by 26% (relative risk(RR) 0.74, 95% confidence interval(CI), 0.69–0.79) and 60% (0.40, 0.36–0.45) respectively in those screened, and they were reduced by 15% (0.85, 0.82–0.89) and 33% (0.67, 0.63–0.71) respectively in those invited to screening. Conclusion Among individuals aged 40–69 years in high risk areas of esophageal cancer, one-time endoscopic screening program was associated with a significant decrease in esophageal cancer incidence and mortality.