Higher Risk Of Esophageal Cancer Research Articles

Esophageal cancer in Hispanics: a demographic analysis of the National Cancer Database

BackgroundHispanics are the fastest-growing minority and the second largest ethnic group in the United States, accounting for 18% of the national population. The American Cancer Society estimated 18,440 new cases of esophageal cancer (EC) in the United States in 2020. Hispanics are reported to be at high risk of EC. We sought to interrogate the demographic patterns of EC in Hispanics. Secondary objective was to examine evidence of socioeconomic disparities and differential therapy. MethodsWe identified Hispanic vs non-Hispanic patients with EC in the National Cancer Database between 2005 and 2015. Groups were statistically equated through propensity score-matched analysis. ResultsA total of 3205 Hispanics (3.8%) were identified among 85,004 patients with EC. We identified significant disparities between Hispanic and non-Hispanic groups. Disparities among Hispanics included higher prevalence of squamous EC, higher likelihood of stage IV cancer diagnosis, younger age, uninsured status, and income< $38,000. Hispanics were less likely to have surgical intervention or any type of treatment when compared to non-Hispanics. Multivariate analysis showed that age, ethnicity, treatment, histology, grade, stage, and Charlson–Deyo scores were independent predictors of survival. Treated Hispanics survived longer than non-Hispanics. ConclusionDespite the lower prevalence of EC, there is a disproportionately higher prevalence of metastatic and untreated cases among Hispanics. This disparity may be explained by Hispanics' limited access to medical care, exacerbated by their socioeconomic and insurance status. Further study is warranted to examine these health disparities among Hispanics.

A real-world study was conducted to develop a nomogram that predicts the occurrence of anastomotic leakage in patients with esophageal cancer following esophagectomy.

The incidence of anastomotic leakage (AL) following esophagectomy is regarded as a noteworthy complication. There is a need for biomarkers to facilitate early diagnosis of AL in high-risk esophageal cancer (EC) patients, thereby minimizing its morbidity and mortality. We assessed the predictive abilities of inflammatory biomarkers for AL in patients after esophagectomy. In order to ascertain the predictive efficacy of biomarkers for AL, Receiver Operating Characteristic (ROC) curves were generated. Furthermore, univariate, LASSO, and multivariate logistic regression analyses were conducted to discern the risk factors associated with AL. Based on these identified risk factors, a diagnostic nomogram model was formulated and subsequently assessed for its predictive performance. Among the 438 patients diagnosed with EC, a total of 25 patients encountered AL. Notably, elevated levels of interleukin-6 (IL-6), IL-10, C-reactive protein (CRP), and procalcitonin (PCT) were observed in the AL group as compared to the non-AL group, demonstrating statistical significance. Particularly, IL-6 exhibited the highest predictive capacity for early postoperative AL, exhibiting a sensitivity of 92.00% and specificity of 61.02% at a cut-off value of 132.13 pg/ml. Univariate, LASSO, and multivariate logistic regression analyses revealed that fasting blood glucose ≥7.0mmol/L and heightened levels of IL-10, IL-6, CRP, and PCT were associated with an augmented risk of AL. Consequently, a nomogram model was formulated based on the results of multivariate logistic analyses. The diagnostic nomogram model displayed a robust discriminatory ability in predicting AL, as indicated by a C-Index value of 0.940. Moreover, the decision curve analysis provided further evidence supporting the clinical utility of this diagnostic nomogram model. This predictive instrument can serve as a valuable resource for clinicians, empowering them to make informed clinical judgments aimed at averting the onset of AL.

Uncovering Risks Associated with Smoking Types and Intensities in Esophageal Cancer within High-Prevalence Regions in Africa: A Comprehensive Meta-analysis.

Tobacco is usually cited among the well-known risk factors of esophageal cancer; nevertheless, the extent of the contribution of the type of smoking and its intensity to the disease has not been comprehensively elucidated in Africa. We searched MEDLINE/PubMed, Excerpta Medica Database, Web of Science, Scopus, Cochrane Library, and African Journals Online studies published before September 2023. The quality of the studies was assessed using the Newcastle-Ottawa scale, and the funnel plot was used for assessing potential publication bias. Meta-analyses were conducted to estimate summary effects using random-effects models. This study included 22,319 participants from 27 studies. The results strongly indicate a significant association between tobacco use and a higher risk of esophageal cancer. The risk of esophageal cancer is notably higher among pipe smokers [OR = 4.68; 95% confidence interval (CI), 3.38-6.48], followed by hand-rolled cigarette smokers (OR = 3.79; 95% CI, 2.68-5.35), in comparison with those who smoked commercially manufactured cigarettes (OR = 2.46; 95% CI, 1.69-3.60). Our findings also showed that the risk of esophageal cancer is highest in people smoking >183 packs per year (OR = 5.47; 95% CI, 3.93-7.62), followed by those smoking 93 to 183 packs per year (OR = 3.90; 95% CI, 3.13-4.86), in comparison with those smoking ≤92 packs per year (OR = 2.90; 95% CI, 2.19-3.84). Our findings strongly show that among the different types of tobacco use in Africa, pipe and hand-roller smokers face a higher risk of esophageal cancer.

Oesophageal cancer awareness and anticipated time to help-seeking: results from a population-based survey.

Modifying public awareness of oesophageal cancer symptoms might help to decrease late-stage diagnosis and, in turn, improve cancer outcomes. This study aimed to explore oesophageal cancer symptom awareness and determinants of lower awareness and anticipated time to help-seeking. We invited 18,156 individuals aged 18 to 75 years using random sampling of the nationwide Dutch population registry. A cross-sectional web-based survey containing items adapted from the Awareness and Beliefs about Cancer measure (i.e., cancer symptom awareness, anticipated time to presentation with dysphagia, health beliefs, and sociodemographic variables) was filled out by 3106 participants (response rate: 17%). Descriptive statistics were calculated and logistic regression analyses were performed to explore determinants of awareness and anticipated presentation (dichotomised as <1 month or ≥1 month). The number of participants that recognised dysphagia as a potential symptom of cancer was low (47%) compared with symptoms of other cancer types (change in bowel habits: 77%; change of a mole: 93%; breast lump: 93%). In multivariable analyses, non-recognition of dysphagia was associated with male gender (OR 0.50, 95% CI 0.43-0.58), lower education (OR 0.44, 0.35-0.54), and non-western migration background (OR 0.43, 0.28-0.67). Anticipated delayed help-seeking for dysphagia was associated with not recognising it as possible cancer symptom (OR 1.58, 1.27-1.97), perceived high risk of oesophageal cancer (OR 2.20, 1.39-3.47), and negative beliefs about oesophageal cancer (OR 1.86, 1.20-2.87). Our findings demonstrate a disconcertingly low public awareness of oesophageal cancer symptoms. Educational interventions targeting groups with decreased awareness and addressing negative cancer beliefs may lead to faster help-seeking behaviour, although additional studies are needed to determine the effect on clinical cancer outcomes.

Abstract 3434: Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank

Abstract Introduction: The association between adiposity and cancer risk differs between sexes for some cancer types. Methods: We prospectively examined adiposity in relation to cancer incidence according to sex hormones in the UK Biobank. Adiposity was assessed by body mass index (BMI) and visceral adipose tissue (VAT), the latter predicted using determinants of age, height, weight, hip circumference, waist circumference, and race. Serum sex hormone binding globulin (SHBG), testosterone, and estradiol were measured using a biochemistry assay and were classified as high or low based on median levels. Cancer incidence was ascertained using ICD-10 codes through cancer registry linkage. For cancer types showing a sex difference in the association between adiposity and cancer incidence, we assessed multiplicative and additive interaction with sex hormones in men and women separately and corrected for multiple testing using false discovery rate. We used Cox regression to calculate the multivariable hazard ratio (HR) of cancer per increase between the 90th to 10th percentile of adiposity (BMI or predicted VAT). Results: During a median follow-up of 13.1 years, we documented 23,964 and 21,045 incident cancer cases among 217,460 men and 256,163 women, respectively. Adiposity showed a much stronger association with higher risk of colorectal, esophageal, and liver cancers in men than women. In men, BMI was more strongly associated with higher risk of colorectal cancer in low vs. high levels of SHBG (HR (95%CI) of 1.47 (1.31-1.64) vs. 1.12 (0.94-1.33) (adjusted Pinteraction = 0.027). In contrast, BMI showed a stronger association in high vs. low levels of SHBG with esophageal (HR = 2.39 vs. 1.62) and liver cancers (HR = 3.24 vs 1.96) in men (adjusted Pinteraction = 0.038 and 0.027, respectively). Among women, BMI was associated with a higher risk of esophageal cancer in those with low SHBG (HR=1.68) but not in those with high SHBG (HR=0.64) (adjusted Pinteraction = 0.025). Similar patterns were observed for predicted VAT. Men with high SHBG levels and high adiposity (BMI and predicted VAT) had 7.63 (5.08-11.46) and 8.92 (5.72 to 13.90), respectively, times higher risk of liver cancer compared to men with low SHBG levels and low adiposity. No effect modification by estradiol or testosterone was detected for any of the cancers studied. Conclusions: The association between adiposity and colorectal, esophageal, and liver cancer differed by sex. SHBG may be an important factor underlying these differences. Citation Format: LeeAnn Lucas, Yujia Lu, Edward L. Giovannucci, Mingyang Song. Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3434.

Immune-Related Long Non-Coding RNA Signature Determines Prognosis and Immunotherapeutic Coherence in Esophageal Cancer.

Aim of this study was to explore the immune-related lncRNAs having prognostic role and establishing risk score model for better prognosis and immunotherapeutic coherence for esophageal cancer (EC) patients. To determine the role of immune-related lncRNAs in EC, we analyzed the RNA-seq expression data of 162 EC patients and 11 non-cancerous individuals and their clinically relevant information from the cancer genome atlas (TCGA) database. Bioinformatic and statistical analysis such as Differential expression analysis, co-expression analysis, Kaplan Meier survival analysis, Cox proportional hazards model, ROC analysis of risk model was employed. Utilizing a cutoff criterion (log2FC > 1 + log2FC < -1 and FDR < 0.01), we identified 3737 RNAs were significantly differentially expressed in EC patients. Among these, 2222 genes were classified as significantly differentially expressed mRNAs (demRNAs), and 966 were significantly differentially expressed lncRNAs (delncRNA). Through Pearson correlation analysis between differentially expressed lncRNAs and immune related-mRNAs, we identified 12 immune-related lncRNAs as prognostic signatures for EC. Notably, through Kaplan-Meier analysis on these lncRNAs, we found the low-risk group patients showed significantly improved survival compared to the high-risk group. Moreover, this prognostic signature has consistent performance across training, testing and entire validation cohort sets. Using ESTIMATE and CIBERSORT algorithm we further observed significant enriched infiltration of naive B cells, regulatory T cells resting CD4+ memory T cells, and, plasma cells in the low-risk group compared to high-risk EC patients group. On the contrary, tumor-associated M2 macrophages were highly enriched in high-risk patients. Additionally, we confirmed immune-related biological functions and pathways such as inflammatory, cytokines, chemokines response and natural killer cell-mediated cytotoxicity, toll-like receptor signaling pathways, JAK-STAT signaling pathways, chemokine signaling pathways significantly associated with identified IRlncRNA signature and their co-expressed immune genes. Furthermore, we assessed the predictive potential of the lncRNA signature in immune checkpoint inhibitors; we found that programed cell death ligand 1 (PD-L1; P-value = .048), programed cell death ligand 2 (PD-L2; P-value = .002), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3; P-value = .045) expression levels were significantly higher in low-risk patients compared to high-risk patients. We believe this study will contribute to better prognosis prediction and targeted treatment of EC in the future.

Elucidating the Link: Chronic Obstructive Pulmonary Disease and the Complex Interplay of Gastroesophageal Reflux Disease and Reflux-Related Complications.

Background and Objective: Presenting chronic obstructive pulmonary disease (COPD) patients frequently report concurrent symptoms of gastroesophageal reflux disease (GERD). Few studies have shown a correlation between GERD and COPD. We aimed to examine the correlation between GERD and COPD as well as secondary related reflux complications, such as esophageal stricture, esophageal cancer, and Barrett's esophagus. Methods: This population-based analysis included 7,159,694 patients. Patients diagnosed with GERD with and without COPD were compared to those without GERD. The enrollment of COPD included centrilobular and panlobular emphysema and chronic bronchitis. Risk factors of COPD or GERD were used for adjustment. Bivariate analyses were performed using the chi-squared test or Fisher exact test (2-tailed) for categorical variables as appropriate to assess the differences in the groups. Results: Our results showed that COPD patients had a significantly higher incidence of GERD compared to those without COPD (27.8% vs. 14.1%, p < 0.01). After adjustment of demographics and risk factors, COPD patients had a 1.407 times higher risk of developing non-erosive esophagitis (p < 0.01), 1.165 higher risk of erosive esophagitis (p < 0.01), 1.399 times higher risk of esophageal stricture (p < 0.01), 1.354 times higher risk of Barrett's esophagus without dysplasia (p < 0.01), 1.327 times higher risk of Barrett's esophagus with dysplasia, as well as 1.235 times higher risk of esophageal cancer than those without COPD. Conclusions: Based on the evidence from this study, there are sufficient data to provide convincing evidence of an association between COPD and GERD and its secondary reflux-related complications.

Disparities in oesophageal cancer risk by age, sex, and nativity in Kuwait:1980–2019

BackgroundThis cross-sectional cohort study assessed the inequalities in oesophageal carcinoma risk by age, sex and nativity in Kuwait: 1980–2019.MethodsUsing oesophageal cancer incidence data from the Kuwait National Cancer Registry, relevant Kuwaiti population data and World Standard Population as a reference, age-standardized incidence rates (ASIR) (per 100,000 person-years) overall and by subcohorts were computed. The incident oesophageal cancer cases count was overdispersed with excessive structural zeros, therefore, it was analyzed using multivariable zero-inflated negative binomial (ZINB) model.ResultsOverall ASIR of oesophageal cancer was 10.51 (95% CI: 6.62-14.41). The multivariable ZINB model showed that compared with the younger age category (< 30 years), the individuals in higher age groups showed a significant (p < 0.001) increasing tendency to develop the oesophageal cancer. Furthermore, compared with the non-Kuwaiti residents, the Kuwaiti nationals were significantly (p < 0.001) more likely to develop oesophageal cancer during the study period. Moreover, compared with 1980-84 period, ASIRs steadily and significantly (p < 0.005) declined in subsequent periods till 2015-19.ConclusionsA high incidence of oesophageal cancer was recorded in Kuwait, which consistently declined from 1980 to 2019. Older adults (aged ≥ 60 years) and, Kuwaiti nationals were at high risk of oesophageal cancer. Focused educational intervention may minimize oesophageal cancer incidence in high-risk groups in this and other similar settings. Future studies may contemplate to evaluate such an intervention.

S388 Risk of Esophageal Cancer in Achalasia: A Matched Cohort Study Utilizing the Veterans Affairs Achalasia Cohort (VA-AC)

Introduction: Achalasia is a postulated risk factor for esophageal cancer (EC) – both squamous cell carcinoma (SCC) and adenocarcinoma (AC). Evaluation of EC-associated risk factors and outcomes in achalasia are limited due to a lack of large, validated cohorts available for study. Our aim was to evaluate the risk of EC among individuals with compared to without achalasia utilizing a large, validated achalasia cohort: the Veterans Affairs Achalasia Cohort (VA-AC). Methods: We conducted a matched cohort study among US Veterans aged ≥18 years between 1999-2020. Individuals with achalasia from the VA-AC were matched to individuals without achalasia at a ratio of 1:4 on index achalasia encounter date, and by sex, year of birth, and first VA visit date +/- 180 days. Follow-up was censored at the outcome (EC), death from a non-EC related cause, or end of the study period. EC cases were ascertained from cancer registry and cause-specific mortality, with all cancer cases reviewed for verification. Descriptive statistics were performed for baseline characteristics. EC hazard functions were assessed using Cox regression models. Results: 1,866 Veterans with achalasia were matched to 7,464 Veterans without achalasia. Median age was 55 years (IQR 48-63), and 92% were male (Table). There were 17 EC cases among Veterans with achalasia (3 AC, 12 SCC, 2 unknown type) compared to 15 EC cases among Veterans without achalasia (11 AC, 1 SCC, 3 unknown). Median time from achalasia diagnosis to EC development was 3.0 years (IQR 1.3-9.1). Patients with achalasia had a 5.4-fold higher risk of EC (HR 5.4, 95% CI 2.8,10.5) compared to patients without achalasia. Higher cumulative incidence of EC (p< 0.0001, based on log-rank test; Figure) in those with vs without achalasia at 5-, 10- and 15-years follow-up was observed. In post hoc analysis, several individuals with EC also had candida esophagitis preceding their cancer diagnosis (12.5%) by median time 1.3 years (IQR 0.2-2.7). Based on univariate cox regression model, patients with vs without candida esophagitis had a 18.3-fold higher risk of EC (95% CI 6.2, 53.7). Conclusion: Using a national cohort of US Veterans, we found achalasia was associated with 5-fold increased EC risk compared to those without achalasia. Candida esophagitis exposure may also predict higher EC risk. Additional studies are needed to understand if this increased risk of EC warrants routine endoscopic surveillance in individuals with achalasia.Figure 1.: Cumulative Incidence of Esophageal Cancer Kaplan Meier curve demonstrating cumulative incidence at 5-, 10- and 15-year time points. Incidence at each time point was significantly higher for individuals with achalasia compared to individuals without achalasia. Table 1. - Achalasia ^ N = 1866 No AchalasiaN = 7464 Age, median (IQR) 55.0 (48.0 – 63.0) 55.0 (48.0 – 63.0) Males, n (%) 1725 (92.4) 6900 (92.4) Race/Ethnicity, n (%) Asian/Pacific Islander 23 (1.2) 113 (1.5) Black 378 (20.3) 1164 (15.6) Hispanic 125 (6.7) 326 (4.4) Multiracial/Other 25 (1.3) 157 (2.1) White 1208 (64.7) 4755 (63.7) Unknown 107 (10.1) 949 (12.7) BMI, median (IQR) 28.6 (25.1 – 32.9) 28.6 (25.4 – 32.6) Diabetes, n (%) 528 (28.3) 1686 (22.6) Smoking Status, n (%) Current 532 (28.5) 1592 (21.3) Former 386 (20.7) 1293 (17.3) Never 556 (29.8) 2398 (32.1) Unknown 392 (21.0) 2181 (29.2) Aspirin Exposure, n (%) 683 (36.6) 1699 (22.8) Barrett’s Esophagus, n (%) 125 (6.7) 189 (2.5) Candida Esophagitis, n (%) 64 (3.4) 7 (0.1) Esophageal Cancer, n (%) 17 (0.9) 15 (0.2) Squamous Cell Carcinoma 12 1 Adenocarcinoma 3 11 Unknown 2 3 *All variables are significant with p-value <.0001, except Age (Matched), Gender (Matched), and BMI which were not statistically significant at alpha=0.05.^Achalasia subjects were previously validated using an algorithm consisting of 3 or more ICD9 or ICD10 codes in a subject's lifetime plus a CPT code for esophageal manometry; the positive predictive value (PPV) for this algorithm to diagnose true achalasia subjects was 94% (95% confidence lower bound of 88.5%) BMI = body mass index; IQR = interquartile range.

Fuzzy Data Mining and Bioinformatics Analysis in Methylation Analysis of M6A Gene Promoter Region in Esophageal Cancer

This work was aimed at analyzing the correlation between the methylation level of the M6A gene in esophageal cancer (EC) and the prognosis of patients based on bioinformatics technology and evaluating the prognostic predictive values of different data mining models. 80 EC patients and 80 healthy people were selected, and the serum of the patients was collected to detect the level of DNA methyltransferase. During the radical resection of EC, tumor tissues and adjacent normal tissues were collected from patients to detect the methylation level of the M6A gene. COX regression analysis was employed to analyze the independent risk factors (IRFs) of M6A gene methylation and other treatments affecting the prognosis of EC patients. The particle swarm optimization (PSO) algorithm was introduced to improve the fuzzy C -means clustering (FCM) algorithm. The differences in the prognostic prediction efficiency of logistic regression analysis (LRA), decision tree (DT) C5.0, artificial neural network (ANN), support vector machine (SVM), and improved FCM (IFCM) models were compared. The levels of DNA methyltransferase and human histone deacetylase 1 (HSD-1) in EC patients were increased greatly ( P &lt; 0.05 ). The methylation rates and methylation levels of M6A methylation regulators (ALKBH5, HNRNPC, METTL3, WTAP, RBM15, YTHDC1, YTHDF1, and FTO) in EC tissues were obviously higher ( P &lt; 0.05 ). The survival time of high-risk EC patients was much shorter than that of low-risk patients ( P &lt; 0.05 ). Univariate and multivariate COX regression analysis showed that gender, tumor grade, TNM grade, degree of infiltration, and methylation of ALKBH5, HNRNPC, and METTL3 genes were IRFs for the prognosis of EC patients ( P &lt; 0.05 ). The areas under the ROC curve (AUCs) of LRA, DT C5.0, ANN, SVM, and IFCM algorithms for predicting the prognosis of patients were 0.813, 0.857, 0.895, 0.926, and 0.958, respectively, and the IFCM model had the best diagnostic effect. In conclusion, the detection of bioinformatics technology showed no obvious DNA methylation in EC patients, and the elevated levels of M6A methylation regulators in patients were an IRF affecting the prognosis of patients. In addition, the fuzzy data mining model can be undertaken as the preferred method for prognosis prediction of EC patients.

Comparison of Secular Trends in Esophageal Cancer Mortality in China and Japan during 1990-2019: An Age-Period-Cohort Analysis.

Esophageal cancer is a prevalent and often fatal malignancy all over the world, with China and Japan bearing a disproportionately high burden. Consequently, we explored and compared the long-term changes in esophageal cancer mortality in China and Japan from 1990 to 2019 to see if there were any etiological clues. From 1990 to 2019, data on mortality in China and Japan were gathered from the Global Burden of Disease Study 2019 (GBD 2019). The age-period-cohort (APC) model was utilized to evaluate the effects of age, period, and cohort. Between 1990 and 2019, the age-standardized mortality rates (ASMRs) for esophageal cancer fell in both nations, with China showing a tremendous reduction after 2005. The overall net drifts per year were more impressive in China (−5.22% [95% CI, −5.77 to −4.68] for females, −1.98% [−2.22 to −1.74] for males) than in Japan (−0.50% [−0.91 to −0.08] for females, −1.86% [−2.12 to −1.59] for males), and the local drift values in both countries were less than zero in all age groups for both sexes. The longitudinal age curves of esophageal cancer mortality increased as age advances and the sex disparity gradually exacerbates with age. The period and cohort effects were uncovered to have similar declining patterns for both sexes in both nations; however, the improvement of cohort effects for China’s younger generation has stagnated. The ASMRs, period effects, and cohort effects have decreased for both countries and sexes over the 1990–2019 period. The decline in cohort effects for China’s younger generation has plateaued, possibly due to the rising rates of smoking and obesity among Chinese youngsters. Comprehensive population-level treatments aimed at smoking cessation, obesity prevention, and gastrointestinal endoscopy screening should be carried out immediately, particularly for men and older birth cohorts at a higher risk of esophageal cancer.

Impacts of ADH1B rs1229984 and ALDH2 rs671 polymorphisms on risks of alcohol-related disorder and cancer.

ADH1B rs1229984 and ALDH2 rs671 are the specifically prevalent functional variants in the East Asians. These variants, which result in a dramatic change in enzyme activity, are highly associated with alcohol-related disorders and cancer. Previous studies focusing on the additive and synergic effects of the variants are few and inconsistent. The aim of the research was to evaluate the associations of ADH1B rs1229984 and ALDH2 rs671 with the risks of alcohol-related disorder and cancer. This cohort study enrolled 42,665 participants from the Taiwan Precision Medicine Initiative database, including 19,522 and 20,534, ADH1B and ALDH2 carriers, respectively. The associations between the two variants and cancer risk were analyzed by univariable and multivariable logistic regression. Compared with the noncarriers, the ADH1B rs1229984 variant had a stronger effect on alcohol-related disorders and was related to an increased risk of alcohol-related cancers. The CC genotype of ADH1B rs1229984 was significantly associated with cancer of the larynx, pharynx, and nasal cavities [odds ratio (OR)=1.56, p=0.0009], cancer of the pancreas (OR=1.66, p=0.018), and cancer of the esophagus (OR=4.10, p < 0.001). Participants who carried the rs1229984 TC/CC and rs671 GG genotypes were at higher risk of esophageal cancer (OR=3.02, p < 0.001). The risk of esophageal cancer was increased by 381% (OR=4.81, p < 0.001) in those carrying the rs1229984 TC/CC and rs671 GA/AA genotypes. rs1229984 and rs671 are common and functionally important genetic variants in the Taiwanese population. Our findings provide strong evidence of additive and synergic risks of ADH1B and ALDH2 variants for alcohol-related disorders and cancer. The results suggested that are reduction in alcohol consumption should be advised as a preventive measure for high-risk patients carrying ADH1B rs1229984 C or the ALDH2 rs671 A allele.

Artesunate Inhibits the Development of Esophageal Cancer by Targeting HK1 to Reduce Glycolysis Levels in Areas With Zinc Deficiency.

Esophageal cancer (EC) threatens many lives in China, especially in areas with high incidences of EC. Our previous studies proved that zinc deficiency (ZD) promotes the cell cycle, thus promoting the progression of EC in areas with a high incidence of EC. Artesunate could inhibit the cell cycle, thereby inhibiting the progression of EC. In this study, we first demonstrated the mechanism by which artesunate inhibits EC in vitro and then demonstrated that artesunate could reverse the ZD-promoted progression of EC before EC occurred in vivo. The results showed that artesunate could inhibit the cell cycle, metastasis, and glycolysis of EC cells. Artesunate could target HK1, promote HK1 degradation, and reduce the levels of HIF-1α and PKM2 expression, which are key glycolysis enzymes. The in vivo results showed that ZD could increase the expression of HK1 and increase the incidence of EC. Artesunate reduced the incidence of EC and decreased the level of HK1 expression before EC occurred. Artesunate has an anti-EC effect by inhibiting aerobic glycolysis and has the potential to be a drug that prevents EC in areas with a high risk of EC.

Mortality Risk factors and SOX2 and mTOR expression in Patients with Esophageal Cancer.

Causes of mortality in EC patients are not confined to cancer-specific mortality but include various protein expressions of SOX2 and mTOR in Esophageal Cancer patients and their correlation with the clinical stage. Data about the risk factors and involvement of cancer-specific protein are still lacking. This study aimed to define the risk factors and association of SOX2 and mTOR expression in mortality in patients with EC. We conducted a retrospective cohort study to assess the risk factors for cancer-specific mortality and cardiovascular mortality in patients with esophageal cancer (EC). The expression rates of SOX2, as well as MTO, were checked in patients. The multivariate analysis revealed a high-risk EC mortality with age ≥ 65 years, black race, grade, stage, and sequence of treatment; radiation after surgery; radiation before and after surgery; Surgery both before and after radiation. While the cardiovascular mortality increased with age ≥ 65 years, adenocarcinoma type, grade, stage, and sequence of treatment. The expression rates of SOX2, as well as mTOR, were 75.5 percent and 86.8 percent in Esophageal Cancer, while were 10.7 percent and 7.5 percent in osteochondroma, respectively, which was statistically significant (P<0.05). Risk factors for cancer-specific mortality and cardiovascular mortality in EC patients include older age at diagnosis, male sex, non-married status, grade III of the tumor, the regional or distant spread of the tumor, no cancer-directed therapy. The expression levels of SOX2, mTOR, and the total survival time were related to the different stages. It shows an upward trend for the expression levels of mTOR and SOX2 in Esophageal Cancer tissues. The expression levels of SOX2 and mTOR are related to the clinical stage, metastasis, and prognosis.

Subsequent Malignant Neoplasms of the Gastrointestinal Tract after Blood or Marrow Transplantation - a BMTSS Report

Background and Purpose: Subsequent malignant neoplasms (SMNs) are a leading cause of non-relapse mortality after blood or marrow transplantation (BMT). Cancers of the gastrointestinal (GI) tract are of special interest since their clinical behavior is often aggressive, but early detection through screening is possible for specific GI malignancies. There is limited information regarding the risk of GI SMNs following BMT. The purpose of this study was to report the risk of GI SMNs after BMT and to identify specific exposures associated with increased risk.Materials and Methods: The BMT Survivor Study (BMTSS) is a multi-institutional retrospective cohort study of patients transplanted between 1974 and 2014, with survival ≥2y. Disease and treatment characteristics were obtained from institutional databases and medical records. GI SMNs were identified by review of the BMTSS survey or death records and confirmed by pathology report and/or medical record review. Standardized incidence ratios (SIRs) were calculated to determine excess risk of GI SMNs compared with the general population. Fine-Gray competing risks models examined the association between treatment exposures and GI SMNs.Results: Clinical/demographic characteristics of the cohort are provided in Table 1. The 6,710 BMT recipients in this cohort contributed 62,479 person-years of follow-up, yielding 148 patients with GI SMNs occurring a median of 8.9y (range, 0.3-36.6y) from BMT. The GI SMNs in the cohort included colorectal (n=45), liver (n=36), pancreatic (n=27), esophageal (n=22), gastric (n=11), and other GI (n=7) cancers. By age 70, the cumulative incidence of a GI SMN was 4.8% for allogeneic BMT recipients vs. 1.9% for autologous BMT recipients (p<0.0001, Fig 1). The SIR for a GI SMN after BMT was 1.95 for allogeneic BMT recipients vs. 1.03 for autologous BMT recipients (p=0.8). The risk of esophageal (SIR=3.19, p<0.01), liver (SIR=3.06, p<0.01) and pancreatic cancer (SIR=1.79, p<0.01) was increased when compared to the general population whereas the risk for gastric (SIR=1.15, p=0.6) and colorectal cancers (SIR=0.86, p=0.3) was not. Radiation exposure: Exposure to TBI at age <30y was associated with significantly higher risk for colorectal (SIR=2.67, p=0.003), stomach (SIR=5.16, p=0.005), and liver (SIR=11.61, p<0.001) cancers; the risks were not elevated when TBI exposure occurred at age >60 (Fig 2). The cumulative incidence of GI SMNs by age 70 was significantly higher (p<0.0001) among patients who received high-dose TBI (≥8Gy: 4.8%) vs. those who received low-dose TBI (<8Gy: 2.5%) or no TBI (2.1%) (Fig 3). High-dose TBI (and not low-dose) was associated with a 2.5-fold higher risk of colorectal cancer (95%CI=1.3-4.7). Pre-BMT abdominal radiation was associated with 9.55-fold increased risk of GI SMN (95%CI=2.5-36.5) among allogeneic BMT recipients; the association was primarily driven by pancreatic and esophageal cancer. Chemotherapeutic agents: Pre-BMT anthracyclines (HR=4.84, 95%CI=1.2-20.4) and etoposide conditioning (HR=2.87, 95%CI=1.6-5.3) were associated with an increased risk of liver cancer. Cytarabine conditioning was associated with increased risk of colorectal cancer (HR=3.08, 95%CI=1.4-6.9). Chronic GvHD: Risk of esophageal cancer was 9.6-fold higher among allogeneic BMT recipients with chronic GvHD (95%CI=3.3-28.4), when compared with those who received an autologous BMT.Conclusions: This study provides evidence that allogeneic BMT survivors are at increased risk for developing GI SMNs in the setting of specific pre-BMT and BMT-related therapeutic exposures and chronic GvHD. In particular, exposure to myeloablative doses of TBI at age <30y and conditioning with cytarabine and etoposide were associated with increased risk. In addition, pre-BMT exposure to abdominal radiation and anthracyclines were associated with specific types of GI SMNs. These findings and the very high risk of esophageal cancer among those with chronic GvHD provide a framework for developing personalized screening recommendations for those at highest risk. [Display omitted] DisclosuresMcDonald: Varian Medical Systems: Consultancy, Research Funding. Weisdorf: Fate Therapeutics: Research Funding; Incyte: Research Funding. Forman: Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company; Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Allogene: Consultancy. Arora: Syndax: Research Funding; Pharmacyclics: Research Funding; Kadmom: Research Funding.

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.

Psychosocial risk factors associated with esophageal cancer in Chinese cohort: A systematic review and meta-analysis.

Previous studies were controversial about the role of psychosocial factors in the pathogenesis of esophageal cancer (EC). This study aimed to systematically evaluate the effect size of psychosocial risk factors for EC in Chinese cohort.A literature search was conducted in both English and Chinese databases, and odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled using a random-effects model.28 studies were identified with a total of 6951 EC cases and 7469 controls. The meta-analysis indicated a higher risk of EC among the individuals with psychological trauma (OR: 2.36, 95% CI: 1.71–3.26), Type A behavior (OR: 1.40, 95% CI: 1.17–1.67), depression (OR: 4.00, 95% CI: 2.44–6.55), melancholy (OR: 2.06, 95% CI: 1.32–3.20), always in sulks (OR: 2.49, 95% CI: 1.21–5.12), and irritable personality (OR: 2.13, 95% CI: 1.58–2.89). A lower EC risk was found in the individuals with good interpersonal relationship (OR: 0.35, 95% CI: 0.17–0.70) and outgoing personality (OR: 0.39, 95% CI: 0.19–0.78).This meta-analysis suggested a potential association between psychosocial factors and EC risk. For the individuals with psychosocial risk factors, physicians should pay more attention to EC screening.

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.

Artificial intelligence diagnostic system predicts multiple Lugol-voiding lesions in the esophagus and patients at high risk for esophageal squamous cell carcinoma.

It is known that an esophagus with multiple Lugol-voiding lesions (LVLs) after iodine staining is high risk for esophageal cancer; however, it is preferable to identify high-risk cases without staining because iodine causes discomfort and prolongs examination times. This study assessed the capability of an artificial intelligence (AI) system to predict multiple LVLs from images that had not been stained with iodine as well as patients at high risk for esophageal cancer. We constructed the AI system by preparing a training set of 6634 images from white-light and narrow-band imaging in 595 patients before they underwent endoscopic examination with iodine staining. Diagnostic performance was evaluated on an independent validation dataset (667 images from 72 patients) and compared with that of 10 experienced endoscopists. The sensitivity, specificity, and accuracy of the AI system to predict multiple LVLs were 84.4 %, 70.0 %, and 76.4 %, respectively, compared with 46.9 %, 77.5 %, and 63.9 %, respectively, for the endoscopists. The AI system had significantly higher sensitivity than 9/10 experienced endoscopists. We also identified six endoscopic findings that were significantly more frequent in patients with multiple LVLs; however, the AI system had greater sensitivity than these findings for the prediction of multiple LVLs. Moreover, patients with AI-predicted multiple LVLs had significantly more cancers in the esophagus and head and neck than patients without predicted multiple LVLs. The AI system could predict multiple LVLs with high sensitivity from images without iodine staining. The system could enable endoscopists to apply iodine staining more judiciously.

The prevalence of esophageal cancer after caustic and pesticide ingestion: A nationwide cohort study.

Habits such as smoking and alcohol drinking and existing esophageal malfunction are considered the main risk factors for esophageal carcinogenesis. Caustic ingestion of acidic or alkaline agents or strong irritants can induce severe esophageal corrosive injury and increase esophageal cancer risk. We studied the relationship between esophageal carcinoma and acute detergent or pesticide poisoning by using nationwide health insurance data. Methodology/Principle findings: We compared a pesticide/detergent intoxication cohort (N = 21,840) and an age- and gender-matched control cohort (N = 21,840) identified from the National Health Insurance Research Database between 2000 and 2011. We used the multivariable Cox proportional model to determine esophageal carcinoma risk. The overall incidence density of esophageal cancer was 1.66 per 10,000 person-years in the comparison cohort and 4.36 per 10,000 person-years in the pesticide/detergent intoxication cohort. The corresponding adjusted hazard ratio (HR) for esophageal cancer was 2.33 (95% confidence interval [CI] = 1.41-3.86) in the pesticide/detergent intoxication cohort compared with the control cohort. Patients with corrosive and detergent intoxication did not have a higher risk of esophageal cancer (adjusted HR = 0.98, 95% CI = 0.29-3.33) than those without pesticide/detergent intoxication. However, patients with pesticide intoxication had a significantly higher risk of esophageal cancer (adjusted HR = 2.52, 95% CI = 1.52-4.18) than those without pesticide/detergent intoxication. Conclusion: In the present study, after adjusting for conventional risk factors, we observed that pesticide intoxication could exert substantial effects through increased esophageal cancer risk. However, patients with detergent intoxication may not have an increased risk of esophageal cancer.