Risk Of Esophageal Cancer Research Articles

Association between sulfur microbial diet and the risk of esophageal cancer: a prospective cohort study in 101,752 American adults

BackgroundSulfur microbial diet (SMD) is a dietary pattern closely related to the intestinal load of sulfur-metabolizing microbes in humans. Diet and microbes may play an important role in the carcinogenesis of esophagus. However, epidemiological studies on SMD and esophageal cancer (EC) risk are scarce. Here, we evaluated this association based on a large American cohort.MethodsIn the cohort of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a SMD score was calculated to evaluate participants’ compliance of SMD pattern, with higher scores presenting greater adherence. Cox hazards regression model was used to explore the association between the SMD score and the incidence of EC, esophageal squamous cell carcinoma (ESCC), and esophageal adenocarcinoma (EA). Subgroup analyses were conducted to figure out potential modifiers interacting with SMD on EC. Sensitivity analyses were used to testify the robustness of our main result.ResultsAmong 101,752 participants, 154 EC cases, consisted of 41 ESCC cases and 97 EA cases, were identified with mean follow-up of 8.9 years. In the fully adjusted model, the highest versus the lowest quartiles of the SMD score were found to be associated with an increased risk of EC and ESCC (EC: HRQ4 vs. Q1: 1.64; 95% CI: 1.05, 2.56; P = 0.016 for trend; ESCC: HRQ4 vs. Q1: 2.37; 95% CI: 1.02, 5.47; P = 0.031 for trend), while not significantly associated with increases risk of EA (HRQ4 vs. Q1: 1.41; P = 0.144 for trend). The main result remained through a series of sensitivity analyses. Subgroup analyses showed a stronger association between SMD and EC in participants with no regular consumption of aspirin (HRQ4 vs. Q1: 1.90; 95% CI: 1.04, 3.47) than in those using aspirin regularly (HRQ4 vs. Q1: 1.37; 95% CI: 0.71, 2.66) (P = 0.008 for interaction).ConclusionAdherence to the SMD pattern may be associated with increased risks of EC and ESCC, particularly for EC in individuals who do not regularly consume aspirin.

Single Nucleotide Polymorphisms (SNPs) in the Shadows: Uncovering their Function in Non-Coding Region of Esophageal Cancer.

Esophageal cancer is a complex disease influenced by genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in non-coding regions of the genome have emerged as crucial contributors to esophageal cancer susceptibility. This review provides a comprehensive overview of the role of SNPs in non-coding regions and their association with esophageal cancer. The accumulation of SNPs in the genome has been implicated in esophageal cancer risk. Various studies have identified specific locations in the genome where SNPs are more likely to occur, suggesting a location-specific response. Chromatin conformational studies have shed light on the localization of SNPs and their impact on gene transcription, posttranscriptional modifications, gene expression regulation, and histone modification. Furthermore, miRNA-related SNPs have been found to play a significant role in esophageal squamous cell carcinoma (ESCC). These SNPs can affect miRNA binding sites, thereby altering target gene regulation and contributing to ESCC development. Additionally, the risk of ESCC has been linked to base excision repair, suggesting that SNPs in this pathway may influence disease susceptibility. Somatic DNA segment alterations and modified expression quantitative trait loci (eQTL) have also been associated with ESCC. These alterations can lead to disrupted gene expression and cellular processes, ultimately contributing to cancer development and progression. Moreover, SNPs have been found to be associated with the long non-coding RNA HOTAIR, which plays a crucial role in ESCC pathogenesis. This review concludes with a discussion of the current and future perspectives in the field of SNPs in non-coding regions and their relevance to esophageal cancer. Understanding the functional implications of these SNPs may lead to the identification of novel therapeutic targets and the development of personalized approaches for esophageal cancer prevention and treatment.

Mediating role of circulating inflammatory proteins in the effect of immune cells on esophageal cancer risk: A Mendelian randomization study.

The immune system and inflammatory processes play crucial roles in the development of esophageal cancer (EC). This study aimed to investigate the causal relationships between 731 immune cell phenotypes, 91 circulating inflammatory proteins, and EC, with a particular focus on the mediating role of circulating inflammatory proteins. Utilizing public genetic data, we applied a 2-sample Mendelian Randomization (MR) method to examine the causal relationships between 731 immune cell phenotypes, 91 circulating inflammatory proteins, and EC. Comprehensive sensitivity analyses were conducted to assess the robustness, heterogeneity, and horizontal pleiotropy of the MR results. Additionally, a 2-step MR method was employed to quantify the impact and proportion of immune cell phenotypes mediated by circulating inflammatory proteins on EC. Eleven immune cell phenotypes and 1 inflammatory cytokine were found to have causal relationships with EC, with results stable across all sensitivity analyses. Mediation analyses revealed that only 2 cell phenotypes had causal relationships with EC through interleukin-10: CD3 on human leukocyte antigen-DR (HLA-DR)+ T cells (mediation effect = -0.009; mediation proportion = 12.01%) and monocytic myeloid-derived suppressor cell absolute count (mediation effect = 0.018; mediation proportion = 18.97%). This study enhances the understanding of the causal relationships between immune cells, circulating inflammatory proteins, and EC. The findings highlight the potential mediating role of interleukin-10, providing new insights into the mechanisms by which immune cells may influence esophageal tumorigenesis.

Esophageal cancer risk is influenced by genetically determined blood metabolites.

It remains unclear what causes esophageal cancer (EC), but blood metabolites have been connected to it. Our study performed a Mendelian randomization (MR) analysis to assess the causality from genetically proxied 1400 blood metabolites to EC level. A two-sample MR analysis was employed to evaluate the causal relationship between 1400 blood metabolites and EC. Initially, the EC genome-wide association study (GWAS) data (from Jiang L et al) were examined, leading to the identification of certain metabolites. Subsequently, another set of EC GWAS data from FINNGEN was utilized to validate the findings. Causality was primarily determined through inverse variance weighting, with additional support from the MR-Egger, weighted median, and MR-PRESSO models. Heterogeneity was assessed using the MR Cochran Q test. The MR-Egger intercept and MR-PRESSO global methods were employed to detect multicollinearity. In this study, Bonferroni corrected P value was used for significance threshold. We found 2 metabolites with overlaps, which are lipids. Docosatrienoate (22:3n3) was found to be causally associated with a decreased risk of EC, as evidenced by the EC GWAS data (from Jiang et al) (odds ratio [OR] = 0.620, 95% confidence interval [CI] = 0.390-0.986, P = .044) and the EC GWAS data (from FINNGEN) (OR = 0.77, 95% CI = 0.6-0.99, P = .042), these results were consistent across both data sets. Another overlapping metabolite, glycosyl-N-(2-hydroxyneuramoyl)-sphingosine, was associated with the risk of ES, with EC GWAS data (from Jiang L et al) (OR = 1.536, 95% CI = 1.000-2.360, P = .049), while EC GWAS data (from FINNGEN) (OR = 0.733, 95% CI = 0.574-0.937, P = .013), the 2 data had opposite conclusions. The findings of this study indicate a potential association between lipid metabolites (Docosatrienoate (22:3n3) and glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1 (2OH))) and the risk of esophageal carcinogenesis.

Gastric Cancer in One-Anastomosis Mini-gastric Bypass: Case Report and Systematic Review.

In the last years, one-anastomosis gastric bypass (OAGB) has been proposed more frequently as obesity surgery technique. Several trials have demonstrated that the easier technical feasibility does not affect the long-term surgical result. However, concern about increased risk of gastric and esophageal cancers has been expressed by several bariatric surgeons. The present study reports the 2nd case of cancer of the gastrointestinal-jejunal anastomosis in a OAGB patient focusing the attention on some technical issues correlated and offering a systematic review of the literature.

Genetically predicted 486 blood metabolites in relation to risk of esophageal cancer: a Mendelian randomization study.

Enhancing therapy choices for varying stages of esophageal cancer and improving patient survival depend on timely and precise diagnosis. Blood metabolites may play a role in either causing or preventing esophageal cancer, but further research is needed to determine whether blood metabolites constitute a genetic risk factor for the disease. In order to tackle these problems, we evaluated the causal association between esophageal cancer and 486 blood metabolites that functioned as genetic proxies using a two-sample Mendelian randomization (MR) study. We utilized two-sample MR analyses to evaluate the causal links between blood metabolites and esophageal cancer. For the exposure, we used a genome-wide association study (GWAS) of 486 metabolites, and a GWAS study on esophageal cancer from Sakaue et al. was used for preliminary analyses. Causal analyses employed randomized inverse variance weighted (IVW) as the main method, supplemented by MR-Egger and weighted median (WM) analyses. Sensitivity analyses included the MR-Egger intercept test, Cochran Q test, MR-PRESSO, and leave-one-out analysis. Additionally, independent esophageal cancer GWAS data were utilized for replication and meta-analysis. FDR correction was applied to discern features with causal relationships. For conclusive metabolite identification, we conducted Steiger tests, linkage disequilibrium score regression, and colocalization analyses. Moreover, we utilized the program MetaboAnalyst 5.0 to analyze metabolic pathways. This study found an important association between esophageal cancer and three metabolites: 1-linoleoylglycerophosphoethanolamine* [odds ratio (OR) = 3.21, 95% confidence interval (CI): 1.42-7.26, p < 0.01], pyroglutamine* (OR = 1.92, 95% CI: 1.17-3.17, p < 0.01), and laurate (12:0) (OR = 3.06, 95% CI: 1.38-6.78, p < 0.01). This study establishes a causal link between three defined blood metabolites and esophageal cancer, offering fresh insights into its pathogenesis.

Association Between Type 1 Diabetes Mellitus and Incident Gastrointestinal Cancer in Korean Population: A Nationwide Retrospective Cohort Study.

The age-standardised incidence ratio of gastrointestinal cancers in type 1 diabetes (T1D) patients has been reported to be higher than that in the general population. After adjusting for shared risk factors, we aimed to explore the association between T1D and gastrointestinal cancer and examine how this relationship varies by age and sex. This retrospective cohort study included 268,179 participants from the Korean National Health Insurance Service-National Sample Cohort. The primary outcome is the incident of gastrointestinal cancers, based on diagnostic codes. Multivariate Cox regression analyses were performed to assess the association between T1D and gastrointestinal cancers. Of the 268,179 participants, 2681 had T1D at baseline and were followed for 12.98 (± 2.92) years. Compared with non-T1D, T1D patients had a significantly increased risk of all gastrointestinal cancer (adjusted hazard ratio [aHR]: 1.403, 95% confidence interval [CI]: 1.253-1.573). T1D patients increased risks of oesophageal cancer (aHR: 1.864, 95% CI: 1.038-3.349), gastric cancer (aHR: 1.313, 95% CI: 1.066-1.616), colon cancer (aHR: 1.365, 95% CI: 1.110-1.678), liver cancer (aHR: 1.388, 95% CI: 1.115-1.727), and pancreatic cancer (aHR: 1.716, 95% CI: 1.182-2.492). The consistency of this association persisted among both male and female, with its strength increasing with older age. The risk of gastrointestinal cancer was significantly increased in T1D patients. Older male T1D patients exhibit a higher risk, suggesting the need for targeted attention in their care.

S727 GLP-1 RA Use in Patients with T2DM is Associated with Lower Risk of Esophageal Cancer: A National Analysis

S727 GLP-1 RA Use in Patients with T2DM is Associated with Lower Risk of Esophageal Cancer: A National Analysis

S605 Cholecystectomy Is Associated With Reduced Risk of Esophageal Cancer: A Multi-Center Research Network Study

S605 Cholecystectomy Is Associated With Reduced Risk of Esophageal Cancer: A Multi-Center Research Network Study

S699 GLP-1 Receptor Agonists Are Associated With Decreased Esophageal Cancer Risk in Type 2 Diabetes Patients Compared to Other Anti-Diabetic Therapy

S699 GLP-1 Receptor Agonists Are Associated With Decreased Esophageal Cancer Risk in Type 2 Diabetes Patients Compared to Other Anti-Diabetic Therapy

Risk of Esophageal and Gastric Cancer in Patients with Type 2 Diabetes Receiving Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs): A National Analysis.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety. We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of >25 kg/m2, and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients' baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark. A total of 2,748,431 patients with T2DM were identified. Of those, 6% (n = 167,077) were on a GLP-1 RA and 94% (n = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, p < 0.0001) and esophageal cancer (0.04% vs. 0.13%, p < 0.0001) at the seven-year mark. The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies.

Causal association between hyperthyroidism and risk of gastroesophageal reflux or esophageal cancer: a bidirectional Mendelian randomization investigation.

Emerging observational studies indicated an association between hyperthyroidism and gastrointestinal disorders. However, it remains unclear whether this association is causal, particularly in the case of gastroesophageal reflux (GERD) and esophageal cancer. To assess the potential causal relationship between hyperthyroidism and GERD or esophageal cancer, we conducted a bidirectional 2-sample Mendelian randomization study. Independent genetic instruments for hyperthyroidism from the UK Biobank (N case=3,545 and N control=459,388) and public genome-wide association study (GWAS) dataset (N case=3,731 and N control=480,867) were used to investigate the association with esophageal cancer in the UK Biobank study (N case=740 and N control=372,016) and GERD in the public GWAS database (N case=20,381 and N control=464,217). Four different approaches (inverse variance weighted (IVW), weighted mode, MR-Egger, and weighted median regression) were used to ensure that our results more reliable. Additional sensitivity analyses were also performed to validate our results. When hyperthyroidism was considered as the exposure factor, it appeared to act as a protective factor for GERD (ORIVW = 0.88, 95% CI, 0.79-0.99, P = 0.039), while as a risk factor for esophageal cancer (ORIVW = 1.03, 95% CI, 1.01-1.06, P = 0.003). However, there is no evidence supporting a reverse causal relationship between genetic susceptibility to hyperthyroidism and GERD or esophageal cancer. Our findings provided genetic evidence supporting bidirectional causal relationships between hyperthyroidism and GERD or esophageal cancer. These results substantiate certain discoveries from previous observational studies on a causal level and provide insight into relevant genetic susceptibility factors.

Coffee consumption, cancer, and healthy aging: epidemiological evidence and underlying mechanisms.

This comprehensive review examines the role of coffee consumption in promoting healthy aging and its potential impact on cancer prevention. Previous research has shown that moderate coffee intake may contribute to extending healthspan and enhancing longevity through beneficial effects on cardiometabolic health and key biological processes involved in aging. However, the relationship between coffee consumption and cancer risk remains controversial. This review synthesizes longitudinal observational and interventional data on the effects of coffee consumption on overall and site-specific cancers, explores underlying biological mechanisms, and discusses clinical and public health implications. Additionally, the review highlights evidence from Mendelian randomization (MR) studies to assess potential causal relationships. Our findings suggest that coffee consumption is associated with a reduced risk of several cancers, including skin, liver, prostate, and endometrial cancers, and may also lower cancer recurrence rates, particularly in colorectal cancer. These protective associations appear consistent across different demographic groups, with the most significant benefits observed at consumption levels of three or more cups per day. However, evidence is inconclusive for many other cancers, and coffee consumption is consistently linked to an increased risk of lung cancer. MR studies generally do not support a strong causal relationship for most cancers, though some suggest potential protective effects for hepatocellular, colorectal, and possibly prostate cancers, with mixed results for ovarian cancer and an increased risk for esophageal cancer and multiple myeloma. The protective effect of coffee on liver and prostate cancer is supported by both observational and MR studies. The potential anti-cancer benefits of coffee are attributed to its bioactive compounds, such as caffeine, chlorogenic acids, and diterpenes, which possess antioxidant and anti-inflammatory properties. These compounds may reduce oxidative stress, inhibit cancer cell proliferation, induce apoptosis, and modulate hormone levels. The review emphasizes the need for further research to clarify dose-response relationships, causal associations, and the biological mechanisms underlying these associations. While coffee consumption appears to contribute to cancer prevention and healthy aging, caution is warranted due to the increased risk of certain cancers, highlighting the complexity of its health effects.

787. THE CHALLENGE OF GASTRO-ESOPHAGEAL ONCOLOGICAL SURGERY AFTER BARIATRIC PROCEDURES: EXPERIENCE OF A REFERRAL HIGH-VOLUME UPPER GI SURGICAL CENTER

Abstract Background The effectiveness of bariatric surgery for weight loss in morbidly obese patients has been well established and it's becoming more common as many surgeons are trained to perform them safely, even in older patients. Obesity is associated with reflux and hormonal imbalances that increase the risk of Barrett's esophagus, esophageal adenocarcinoma and gastric cancer. Bariatric procedures alter gastric anatomy, vascularization and lymphatic drainage and render subsequent upper gastrointestinal surgery for malignancies a technical challenge, that will present more and more in the future. We present laparoscopic sleeve gastrectomy, gastric bypass and gastric banding conversion to oncological respective surgeries. Methods We retrospectively reviewed the medical records of our referral high-volume center for upper gastrointestinal surgery and identified patients who underwent upper gastrointestinal oncologic surgery from January 1998 to May 2024. We selected all patients who had previously undergone bariatric surgery (laparoscopic sleeve gastrectomy, laparoscopic gastric bypass, gastric banding, or other less common procedures). Three patients met our criteria, and we recorded: demographic characteristics, surgical technique, oncologic surgical outcome, postoperative complications, long-term complications, and oncologic follow-up. Results A hybrid IvorLewis esophagectomy was performed years after a sleeve gastrectomy for distal esophageal adenocarcinoma. The sleeve was used for gastric pull-up, adequately vascularized by the right gastroepiploic artery as demonstrated by intraoperative indocyanine green. A patient developed adenocarcinoma of the cardia after Roux-en-Y gastric bypass, infiltrating the gastric pouch, the gastric remnant and liver S2. After neoadjuvant chemotherapy, an open Ivor-Lewis esophagectomy was performed using the gastric remnant for a pull-up. In a third patient, a locally advanced adenocarcinoma of the stomach developed after gastric banding. After neoadjuvant chemotherapy, an open total gastrectomy with Roux-en-Y esophagojejunostomy was performed. Conclusion We report three cases of successful esophago-gastric oncological surgery in patients with altered anatomy and vascularization due to previous bariatric surgery, without major postoperative complications or mortality. Oncologic benchmarks for both esophageal and gastric surgery were met as a high lymph node yield and oncologic margins were maintained. Our heterogeneous series suggests that sleeve gastrectomy, gastric bypass, and gastric banding surgery can be successfully converted to resective surgeries after a metachronous neoplasia diagnosis in high-volume upper gastrointestinal centers. These and similar modified reconstructive techniques are likely to be used in the future as metabolic surgery and esophago-gastric cancer are increasing.

764. PREDICTING AGE-SPECIFIC PREVALENCE OF BARRETT'S OESOPHAGUS IN AUSTRALIAN AND UNITED STATES

Abstract Background Barrett’s esophagus is the precursor to esophageal adenocarcinoma (EAC). EAC detected from endoscopic surveillance programs accounts for &amp;lt;10% of all EAC, suggesting a large number of patients with Barrett’s esophagus are likely unaccounted for. Several studies have estimated the observed prevalence of Barrett’s esophagus to be approximately 1%, but this may be an underestimate. The aim of this study is to use population incidence of EAC and rate of progression from Barrett’s esophagus from large cohort studies to estimate a realistic prevalence of Barrett’s esophagus. Methods A simple tree cohort model was created for progression to EAC from birth to death (100 years) for American and Australian population. Lifetime risk of esophageal cancer and adenocarcinoma were endpoints. This was then used to back-calculate age-specific and overall prevalence of Barrett’s esophagus using an optimisation algorithm. Results Lifetime risk of esophageal cancer and adenocarcinoma in US Whites is 0.56% and 0.36% respectively, while in Australian population is slightly higher at 0.81% and 0.61% (range 0.57% - 0.65%). Estimated overall prevalence of Barrett’s esophagus is ~3% (±0.3%) and ~5.4% (±0.6%) in US White and Australian populations, while in males is 5.3% (±0.6%) and 7.4% (±0.3%), respectively. Female cohorts were seen to have lower chance of developing esophageal cancer, adenocarcinoma, and Barrett’s esophagus. Conclusion Cohort studies of Barrett’s esophagus are likely to underestimate its prevalence of this silent disease. Computational models based on progression from Barrett’s esophagus to EAC accounting for undetected disease reveal higher estimates, which can help in future screening options.

790. RISK FACTORS FOR ESOPHAGEAL CANCER IN NORTHEAST INDIA: A MULTI-CENTRIC CASE-CONTROL STUDY

Abstract Background Northeast India has a high incidence of esophageal cancer(EC), with age-adjusted incidences ranging from 19 to 50 per 100,000 (in females and males respectively). This is over ten times the average incidence of EC in India. The local preparation of raw betel nut,‘kwai’, is integral to the culture, but its role has not been established. This study aimed to assess the role of betel nut, with or without tobacco as a causative agent for EC. The role of alcohol was also studied. Methods A multi-centric, matched case-control study was performed from October 2022 to March 2024 in three centres situated in the Northeast region of India. All cases of biopsy proven squamous EC, arising from the cricopharynx to the gastroesophageal junction were included, with matched controls (1:3 ratio) being patients visiting the hospital for minor ailments and healthy volunteers from the community. A validated questionnaire was administered by trained trial coordinators. The data was analysed using a conditional multivariate logistic regression which incorporated the individual matching of cases with 3 controls. A p-value of &amp;lt; 0.05 was considered statistically significant. Results A total of 185 cases and 556 controls were matched for age (± 5 years), ethnicity, and gender. There was an increased risk of EC for those consuming betelnut with slaked lime [Calcium hydroxide Ca(OH)2] (Odds Ratio(OR) of 3.77 (Confidence Interval(CI) 1.30-10.92)); alcohol (OR 2.00 CI: 1.80-6.67) and tobacco (OR 3.47 CI:1.80-6.67). The risk was higher for those who swallowed the betel quid and juice as compared with those who spit it out (OR 4.01 CI: 2.24-6.73). The risk was increased in those consuming betelnut while hungry, instead of a meal (OR 10.40 CI 3.66-29.57). The risk was increased in those with no formal education (OR of 4.13 CI: 2.01-8.49). On adjusting with other risk factors (tobacco and alcohol), the risk was highest for betelnut with tobacco (OR 7.84 CI 2.12-29.90) and betelnut with alcohol (OR 2.84 CI 1.11-7.29). All these OR were statistically significant. Conclusion Consumption of betelnut with slaked lime increases the risk of EC. This risk is increased by the concomitant use of tobacco and alcohol.

Association between four insulin resistance surrogates and the risk of esophageal cancer: a prospective cohort study using the UK Biobank

PurposeThis study explored the association between triglyceride-glucose (TyG), TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), metabolic score for insulin resistance (IR) (METS-IR) and the risk of esophageal cancer.MethodsA total of 388,900 participants from the United Kingdom Biobank from 2006 to 2010 were included. Fine-Gray models, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curves were used to assess the association between the four IR surrogates and the risk of esophageal cancer, specifically, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC).ResultsTen years after recruitment, 0.16% (95%CI 0.11–0.26%) had esophageal cancer and 4.17% (95%CI 3.86–4.46%) are deceased. For each standard deviation increase in the TyG index, TyG-BMI, TG/HDL-C, and METS-IR, the risk of EAC increased by Hazard ratios (HR)1.16, 1.37, 1.08, and 1.36, respectively (all P < 0.05), while the risk of ESCC decreased by HRs 0.80, 0.67, 0.77, and 0.65, respectively. RCS analysis indicated that most relationships were nonlinear (P < 0.05). ROC curves showed that METS-IR had a more robust diagnostic efficacy than TyG, TyG-BMI, and TG/HDL-C.ConclusionTyG index, TyG-BMI, TG/HDL-C, and METS-IR were closely associated with the risk of EAC and ESCC. Additionally, METS-IR surpassed the other three IR indices in predicting and diagnosing the risks of EAC and ESCC. The METS-IR is expected to become a more effective metric for identifying populations at early risk of esophageal cancer and for improving risk stratification.

Unraveling the impact of irritability on esophageal diseases: Insights from multivariable Mendelian randomization analysis

BackgroundPrevious studies have suggested a potential association between irritability and the risk of various diseases. However, establishing a causal relationship has remained a significant challenge. To address this issue, we employed Mendelian randomization (MR), a sophisticated approach that leverages genotype data to emulate the conditions of randomized controlled trials. This method enables us to investigate the potential causal link between irritability and the susceptibility to esophageal diseases. MethodsWe conducted an extensive multivariable MR analysis using summary-level data from genome-wide association studies (GWAS) encompassing various esophageal diseases, including gastroesophageal reflux disease (GERD), esophageal cancer (EC), and Barrett's esophagus. Both univariable and multivariable MR analyses were performed to elucidate and confirm the causal association between genetically predicted irritability and the incidence of esophageal diseases. ResultsBased on our primary causal effects model utilizing MR analyses with the inverse-variance weighted (IVW) method, genetically predicted irritability was identified as a risk factor for GERD (OR = 2.413; 95 % CI: 1.678–3.470; P = 2.03E-06) and Barrett's esophagus (OR = 2.306; 95 % CI: 1.042–5.101; P = 0.039). However, irritability was not found to be associated with the risk of EC, even after adjusting for BMI, smoking initiation, and alcohol consumption. ConclusionThe multivariable MR analysis performed in this study demonstrated a causal relationship between irritability and esophageal diseases. It is imperative to acknowledge the need for further large-scale prospective studies to validate these findings.

Correlation between inflammatory cytokines and the likelihood of developing multiple types of digestive system cancers: A Mendelian randomization study

ObjectiveInflammatory cytokines have been linked to digestive system cancers, yet their exact causal connection remains uncertain. Consequently, we conducted a Mendelian randomization (MR) analysis to gauge how inflammatory cytokines are linked to the risk of five prevalent digestive system cancers (DSCs). MethodsWe collected genetic variation data for 41 inflammatory cytokines from genome-wide association studies (GWAS), and the results data for five common diseases from the Finnish database. Our primary analytical approach involved employing the inverse-variance weighted, residual sum (IVW) method, complemented by the MR-Egger method, the weighted median method, simple mode analysis, and weighted mode analysis as supplementary analytical techniques. Furthermore, we conducted multiple sensitivity analyses. ResultsTumor necrosis factor-related apoptosis-inducing ligand (TRAIL), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-18 showed a negative association with the risk of hepatocellular carcinoma. Conversely, TRAIL was inversely linked to the risk of gastric cancer, while IL-16 exhibited a positive correlation with gastric cancer risk. Stem cell factor (SCF) acted as a protective factor against pancreatic cancer. For colorectal cancer, IL-7, IL-9, IL-13, and vascular endothelial growth factor (VEGF) were identified as risk factors. Notably, our results did not indicate a significant correlation between inflammatory cytokines and the risk of esophageal cancer. ConclusionOur research unveils potential connections between 41 inflammatory cytokines and the risk of five common DSCs through a MR analysis. These associations offer valuable insights that could aid in the development of diagnostic biomarkers and the identification of novel therapeutic targets for DSCs.

MFI-11 in Chinese elderly esophageal cancer patients with postoperative adverse outcomes

BackgroundFrailty becomes more pronounced with advancing age, tightly intertwined with adverse clinical outcomes. Across diverse medical disciplines, frailty is now universally recognized as not only a risk factor but also a predictive indicator for unfavorable clinical prognosis.MethodsThis study was a retrospective cohort study that included clinical data from patients (aged ≥ 65 years) with esophageal cancer treated surgically at the First Affiliated Hospital of Anhui Medical University in 2021. For each patient, we calculated their 11-index modified frailty index(mFI-11) scores and categorized the patients into a frailty group (mFI-11hign) and a non-frailty group (mFI-11low) based on the optimal grouping cutoff value of 0.27 from a previous study. The primary study index was the incidence of postoperative pulmonary infection, arrhythmia, anastomotic fistula, chylothorax, and electrolyte disturbance complications. Secondary study indicators included postoperative ICU stay, total hospitalization time, readmission rate within 30 days of discharge, and mortality within 30 days after surgery. We performed univariate and multivariate analyses to assess the association between mFI-11 and adverse outcomes as well as postoperative complications.ResultsFive hundred and fifteen patients were included, including 64.9% (334/515) in the non-frailty group and 35.1% (181/515) in the frailty group. Comparing postoperative complication rates between the two groups revealed lower incidences of postoperative anastomotic fistula (21.5% vs. 4.5%), chylothorax (16.0% vs. 2.1%), cardiac arrhythmia (61.9% vs. 9.9%), pulmonary infections (85.1% vs. 26.6%), and electrolyte disturbance (84.5% vs. 15.0%) in patients of the non-frailty group was lower than that in the frailty group (p < 0.05). mFI-11 showed better prognostic results in predicting postoperative complications. anastomotic fistula (area under the ROC curve AUROC = 0.707), chylothorax (area under the ROC curve AUROC = 0.744), pulmonary infection (area under the ROC curve AUROC = 0.767), arrhythmia (area under the ROC curve AUROC = 0.793), electrolyte disturbance (area under the ROC curve AUROC = 0.832), and admission to ICU (area under the ROC curve AUROC = 0.700).ConclusionPreoperative frail elderly patients with esophageal cancer have a high rate of postoperative complications. mFI-11 can be used as an objective indicator for identifying elderly patients at risk for esophageal cancer.