Association of Body Mass Index and the Risk of Gastro-Esophageal Cancer: A Mendelian Randomization Study in a Japanese Population.

There are growing concerns that body mass index (BMI) is related to cancer risk at various anatomical sites, including the upper gastrointestinal tract, and the existence of a causal relationship remains unclear. The Mendelian randomization (MR) method uses instrumental genetic variables of risk factors to explore whether a causal relationship exists while preventing confounding. In our study, genome-wide association study (GWAS) data from the BioBank Japan (BBJ) project were used. Genetic variants were chosen as instrumental variables using inverse-variance weighting (IVW), MR-Egger regression and weighted-median methods to estimate the causal relationship between BMI and the risk of gastro-esophageal cancer. We found no evidence to support a causal association between BMI and risk of gastric cancer [odds ratio (OR) =0.99 per standard deviation (SD) increase in BMI; 95% confidence interval (CI): (0.76-1.30); P = 0.96] or esophageal cancer [0.78(0.50-1.22); P = 0.28] using the IVW method. Sensitivity analysis did not reveal any sign of horizontal pleiotropy. Additionally, in the gender-stratified analysis, no causal association was found. Findings from this study do not support a causal effect of BMI on gastro-esophageal cancer risk. However, we cannot rule out a modest or nonlinear effect of BMI.

Genetic variant in miR-17-92 cluster binding sites is associated with esophageal squamous cell carcinoma risk in Chinese population.

BACKGROUND: Single nucleotide polymorphisms (SNPs) located in microRNA (miRNA) binding sites can affect the interactions between miRNAs and target genes, which is related to cancer susceptibility and tumorigenesis. However, the association between SNPs located in miR-17-92 cluster binding sites and ESCC risk remains unclear. Therefore, we aimed to explore the relationship between polymorphisms in miR-17-92 cluster binding sites and ESCC susceptibility. METHODS: Six SNPs in the binding sites of miR-17-92 cluster were selected using bioinformatics databases, and their association with ESCC risk was investigated in a case-control study (including 488 cases and 512 controls) based on the population from high incidence areas of ESCC in China. We evaluated the SNP-SNP and SNP-smoking interactions using generalized multifactor dimensionality reduction (GMDR). Moreover, the expression of the miR-17-92 cluster and its target genes was determined in ESCC and adjacent normal tissues by quantitative real-time polymerase chain reaction (qRT-PCR). The dual-luciferase reporter assay was conducted to verify the effect of SNPs on the binding affinity between miRNAs and target genes. RESULTS: We found that the SNP rs1804506 C > T had a significant association with the decreased ESCC risk. The SNP rs1804506 T allele was associated with a significantly decreased risk of ESCC in the additive model (OR = 0.817, 95% CI = 0.681-0.981, P = 0.030). The rs1804506 T allele had more striking effects on reducing ESCC risk in older individuals, female or non-smoker subgroups. We also found a significant interaction effect between rs1366600 and smoking by GMDR methods (P = 0.011). Additionally, the expression levels of miR-19a-3p and TGFBR3 were significantly downregulated in ESCC tissues compared with normal tissues, and the carriers of rs1804506 TT genotype had lower expression level of TGFBR3 than those of rs1804506 CC/CT genotype. Following dual-luciferase reporter assay showed that the rs1804506 T allele reduced the binding of miR-19a-3p and TGFBR3 3'-UTR. CONCLUSIONS: Our findings suggest that the rs1804506 polymorphism in miR-17-92 cluster binding sites contributes to the susceptibility of ESCC, which might provide new clues and scientific evidence for the etiology and biomarkers for the prevention and treatment of ESCC.

Comparative analysis of malnutrition diagnosis methods in lung cancer patients using a Bayesian latent class model.

BACKGROUND AND OBJECTIVES: There are no consensus criteria for malnutrition diagnosis in clinical settings, the Global Leadership Initiative on Malnutrition (GLIM) criteria were developed to facilitate global comparisons of malnutrition prevalence, interventions and outcomes. Validation to assess usefulness in clinical practice is essential, however, the imperfect nature of reference standards used in concurrent validation may result in biased estimates of diagnostic accuracy. The Bayesian latent class model (BLCM) can assess the diagnostic performance when a "gold standard" is absent. This study's objective was to assess the diagnostic performance of the GLIM criteria in comparison with the Nutritional Risk Screening 2002 (NRS-2002) and the Patient Generated Subjective Global Assessment (PG-SGA) in lung cancer patients using a BLCM. We hypothesized that the GLIM criteria are more sensitive and specific for malnutrition diagnosis in lung cancer patients. METHODS AND STUDY DESIGN: 1,384 patient records retrospectively obtained from the "Investigation on Nutrition Status and its clinical outcome of common Cancers" (INSCOC) study were used to determine the prevalence of malnutrition, sensitivity (Se) and specificity (Sp) by applying a BLCM. RESULTS: The prevalence of malnutrition was 0.56. The sensitivity and specificity of the GLIM criteria were Se: 0.85 and Sp: 0.88; Se: 0.74 and Sp: 0.85 for NRS-2002 and Se: 0.96 and Sp: 0.89 for PG-SGA. CONCLUSIONS: Although the GLIM criteria were acceptable for malnutrition diagnosis, PG-SGA is superior for determining cancer-associated malnutrition. Because of its fair sensitivity, NRS-2002 was best equipped to screen out patients not at nutritional risk.

The performance of three nutritional tools varied in colorectal cancer patients: a retrospective analysis.

BACKGROUND AND OBJECTIVE: Nutritional screening tools should be sensitive, simple, and easy to use. Differing opinions among clinicians concern the simplicity of the three tools-the Global Leadership Initiative on Malnutrition (GLIM) criteria, Nutritional Risk Screening 2002 (NRS-2002), and Patient-Generated Subjective Global Assessment (PG-SGA). For each tool, we estimated prediction of overall survival (OS) in tumor staging, sensitivity, and specificity. The NRS-2002 is favored by clinicians because it is simple to use. We compared its sensitivity and specificity with the GLIM and PG-SGA. STUDY DESIGN AND SETTING: This is an analysis of data from 1,358 adult colorectal cancer patients recruited in a multicenter from July 2013 to July 2018. RESULTS: In Kaplan-Meier models, each tool was found to be significantly predictive of OS: NRS-2002 (1.28), GLIM (1.49), and PG-SGA (1.42). Use of any tool improved prediction of survival at tumor staging. NRS-2002 has superior specificity (0.90) to diagnose patients without nutritional deficits (GLIM = 0.62 and PG-SGA = 0.82). CONCLUSION: This study provides evidence for the superiority of NRS-2002 to accurately identify colorectal cancer patients without nutritional limitations. Compared with the complexity of the other tools, NRS-2002 is the simplest tool to use in routine nutritional screening in busy clinical practice.

Dietary patterns and severity of symptom with the risk of esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional latent class analysis.

BACKGROUND: Dietary patterns and symptoms research among Chinese with esophageal squamous cell carcinoma (ESCC) and its precursor lesions is limited, especially as it relates to multiple food consumption and multiple co-occurring symptoms. The aim of our study was to identify the dietary patterns and severity of symptom classes with the risk of esophageal squamous cell carcinoma and its histological precursor lesions, and develop a risk prediction model for different stages of esophageal disease. METHODS: We analyzed data from a multicenter cross-sectional study carried out in ESCC high incidence areas between 2017 and 2018, which included 34,707 individuals aged 40-69 years. Dietary patterns and severity of symptom classes were derived by applying a latent class analysis (LCA). A multiple logistic regression model was used to derive the odds ratio (ORs) and corresponding 95% confidence intervals (CIs) for ESCC and the different stages of esophageal disease according to the dietary patterns and severity of symptom classes identified. We built the risk prediction model by using a nomogram. RESULTS: We identified five dietary patterns and three severity of symptom classes. The dietary patterns were classified as follows: "Healthy", "Western", "Lower consumers-combination", "Medium consumers-combination" and "Higher consumers-combination" patterns based on the intake of foods such as red meat, vegetables and fruits. The severity of symptoms was categorized into "Asymptomatic", "Mild symptoms" and "Overt symptoms" classes based on health-related symptoms reported by the participants. Compared to the "Healthy" pattern, the other four patterns were all associated with an increased risk of esophageal disease. Similarly, the other two symptom classes present different degrees of increased risk of esophageal disease compared to the "Asymptomatic". The nomograms reflect the good predictive ability of the model. CONCLUSION: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results supplied that subjects with diets rich in livestock and poultry meat and low in fruits and vegetables and subjects with typical symptoms were at increased ESCC risk. The findings highlight the importance of considering food and symptom combinations in cancer risk evaluation.

Diagnostic Performance of SGA, PG-SGA and MUST for Malnutrition Assessment in Adult Cancer Patients: A Systematic Literature Review and Hierarchical Bayesian Meta-Analysis.

Because cancer-associated malnutrition is a major health complication, timely nutritional screening is of utmost importance. The aim of this study was to conduct a systematic literature review and meta-analysis of three tools in order to identify the method with the best diagnostic performance. PubMed, EMBASE and Cochrane central register of controlled trials were searched for articles published from database inception to January 2021. Studies that assessed the diagnostic accuracy of the SGA, PG-SGA or MUST in adult cancer patients were included. In order to evaluate the quality of each included study, the QUADAS-2 tool was used after which a meta-analysis was conducted using the hierarchical bivariate model. This model accounts for both within and between study variability. 16 studies (18 datasets) were included to evaluate these tools. The overall sensitivity and specificity for SGA was 0.69 and 0.80, 0.95 and 0.81 for PG-SGA, along with 0.83 and 0.83 for MUST respectively. An assessment of the likelihood ratios showed that PG-SGA had the highest LR + and the lowest LR-, it therefore has the best diagnostic performance to confirm malnutrition in adult cancer patients.

Risk factors for esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional study.

BACKGROUND: Despite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions. METHODS: We performed an endoscopic examination of 44,857 individuals aged 40-69 years from five high incidence regions of China in 2017-2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors. RESULTS: We identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52-3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03-3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05-1.37) was essential risk factor of LGIN. CONCLUSIONS: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

Exposure to outdoor air pollution at different periods and the risk of leukemia: a meta-analysis.

The causes of leukemia remain largely unknown; our aims were to examine the association between the exposure to outdoor air pollution and leukemia risk and to explore the effect of this exposure during different periods of pregnancy and early life. We searched for all case-control and cohort studies published before February 20, 2021, which measured the risk of leukemia in relation to exposure to the air pollutants: particulate matter, benzene, nitrogen dioxide (NO2), and nitrogen oxides (NOx). We then carried out a meta-analysis and calculated the summary relative risks (RRs) of leukemia by using a random-effects model. The potential dose-response relationship was further explored. The results showed that the highest exposure to benzene (RR: 1.20, 95%CI: 1.06-1.35) and NO2 (RR: 1.04, 95%CI; 1.02-1.08) were positively correlated with leukemia risk when compared to the lowest exposure categories for each air pollutant. During pregnancy, exposure to benzene in the third trimester, as well as exposure to NO2 in the second trimester and entire pregnancy, could also increase the risk of leukemia. In the dose-response analysis, benzene exposure and NO2 exposure were linearly associated with the risk of leukemia. Other air pollutants did not have a statistical correlation with leukemia risk. There was a certain degree of publication bias in studies on benzene. Overall, our results support a link between outdoor air pollution and leukemia risk, particularly due to benzene and NO2. Prospero Registration Number: PROSPERO CRD42020207025.

Systematic Identification of circRNA-miRNA-mRNA Regulatory Network in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Circular RNAs (circRNAs) are described as endogenous non-coding RNAs that have been reported to play important roles in the development and progression of cancers. This study aimed to reveal the circRNA-related regulatory mechanism in esophageal squamous cell carcinoma (ESCC). METHODS: A genome-wide circRNA microarray assay was performed to profile the expression of circRNAs in the blood of preoperative ESCC patients and healthy controls. A systematic method of data mining was performed to identify the differentially expressed miRNAs (DEmiRs) and differentially expressed genes (DEGs) based on the metaMA and RankProd analysis. Bioinformatics analyses and multiple tools were employed to construct the potential circRNA-miRNA-mRNA regulatory network. RESULTS: Thirty-three differentially expressed circRNAs were identified in the ESCC blood, including 31 downregulated and two upregulated circRNAs in the blood of ESCC patients compared with the healthy controls. Twenty-three DEmiRs and 2,220 DEGs were obtained by the integration of microarray datasets. An ESCC-associated circRNA-miRNA-mRNA network was constructed based on 31 circRNAs, 3 DEmiRs, and 190 DEGs. Enrichment analyses indicated that the DEGs were associated with a series of biological processes and cancer-related pathways. The protein-protein interaction (PPI) network was generated by the 190 DEGs, with 10 hub genes verified in the network. Subsequently, a sub-network was established for ESCC, which included 29 circRNAs, 2 miRNAs, and 10 hub genes. CONCLUSION: Our study provided a novel clue to help understand the circRNA-miRNA-mRNA regulatory mechanism, highlighting the potential roles of circRNAs in the pathogenesis and development of ESCC.

Nutritional screening tools for adult cancer patients: A hierarchical Bayesian latent-class meta-analysis.

BACKGROUND & AIMS: Cancer treatment requires attentiveness to its broader effect on the body. Cancer's effect on appetite, strength, and body composition is contained in the summary term malnutrition. The tools used to detect malnutrition are a critical part of effective cancer care. In clinical care, selection of any specific tool is random. The relative validity of these tools have not been systematically compared. Using hierarchical Bayesian latent-class meta-analysis methods, this report compares three tools used for adult cancer patients - the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening 2002 (NRS-2002) and the Patient Generated Subjective Global Assessment (PG-SGA). METHOD: Drawing from English and Chinese language databases, a broad pool of eligible studies were identified for further selection and assessment. Using the hierarchical summary receiver operating characteristic (HSROC) model, pooled sensitivity, specificity, and other measurements the accuracy of the three tools were compared. RESULT: A total of 37 eligible studies involving the MNA, NRS-2002 and PG-SGA were included in this meta-analysis. The pooled sensitivity was 0.910 (95% CI: 0.763 to 0.970) for MNA, 0.747 (95% CI: 0.680 to 0.804) for NRS-2002, and 0.964 (95% CI: 0.913 to 0.986) for PG-SGA. The pooled specificity was 0.720 (95% CI: 0.623 to 0.800) for MNA, 0.854 (95% CI: 0.808 to 0.891) for NRS-2002, 0.905 (95% CI: 0.807 to 0.956) for PG-SGA, respectively. The back-calculated likelihood ratio (LR) showed that MNA had a low negative likelihood ratio (LR-), NRS-2002 corresponded to a high positive likelihood ratio (LR+) and PG-SGA represented the best LR+ and LR-. CONCLUSIONS: While there is no standard approach to assessment of malnutrition, the PG-SGA has the best diagnostic performance with cancer patients. Further work is needed to refine the utility of these tools in larger clinical samples.

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

BACKGROUND: Esophageal 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. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: Our 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.