Dataset Information

Association between Serum Level of Multiple Trace Elements and Esophageal Squamous Cell Carcinoma Risk: A Case-Control Study in China.

ABSTRACT: We investigated the associations between multiple serum trace element levels and risk for esophageal squamous cell carcinoma (ESCC). A total of 185 ESCC patients and 191 healthy individuals were recruited in our study. The concentration of 13 trace elements (Al, V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Sr, Cd and Pb) in serum was determined with inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression and the Probit extension of Bayesian Kernel Machine Regression (BKMR) models was established to explore the associations and the cumulative and mixed effects of multiple trace elements on ESCC. Three elements (Zn, Se and Sr) displayed a negative trend with risk for ESCC, and a significant overall effect of the mixture of Al, V, Mn, Ni, Zn, Se and Sr on ESCC was found, with the effects of V, Ni and Sr being nonlinear. Bivariate exposure-response interactions among these trace elements indicated a synergistic effect between Zn and Se, and an impactful difference of V combined with Ni, Sr or Zn. Our results indicate that Ni, V, Al, Mn, Zn, Se and Sr are associated with ESCC risk, providing additional evidence of the complex effects of trace elements disorder during the etiology of EC development.

SUBMITTER: Zhang J

PROVIDER: S-EPMC9455051 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Association between Serum Level of Multiple Trace Elements and Esophageal Squamous Cell Carcinoma Risk: A Case-Control Study in China.

Zhang Jingbing J Wang Geng G Huang Anyan A Cao Kexin K Tan Wei W Geng Hui H Lin Xiaosheng X Zhan Fulan F Wu Kusheng K Zheng Shukai S Liu Caixia C

Cancers 20220831 17

We investigated the associations between multiple serum trace element levels and risk for esophageal squamous cell carcinoma (ESCC). A total of 185 ESCC patients and 191 healthy individuals were recruited in our study. The concentration of 13 trace elements (Al, V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Sr, Cd and Pb) in serum was determined with inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression and the Probit extension of Bayesian Kernel Machine Regression (BKMR) models was es ...[more]

PMID: 36077776

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Project description:Toxic elements exposure and imbalance in essential element homeostasis remain incomprehensive in esophageal squamous cell carcinoma (ESCC) carcinogenesis, especially in tumor progression. To reveal the toxic and essential elements inside body associated with ESCC occurrence, aggressive features and outcomes, whole blood concentrations of eight trace elements were quantified in 150 ESCC cases and 177 controls using inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations of cadmium (Cd), lead (Pb), chromium (Cr), copper (Cu), arsenic (As), and selenium (Se) showed significant differences between the case and control subjects. The restricted cubic spline (RCS) analysis showed As, Zinc (Zn), and manganese (Mn) was linked with ESCC risk in a U-shaped pattern, whereas an inverted U-shaped curve for Cd (all P-non-linear < 0.05). Contrary to Se, the elements Pb, Cr and Cu were positively associated with ESCC risk. By Bayesian Kernel Machine Regression models, the mixtures of the eight trace elements were found to be significantly associated with ESCC risk and metastasis, with Cr, Mn, Cu, Zn, and Pb having a PIP of 1.000 for occurrence risk and Mn being the main contributor for metastatic risk (PIP = .6570). The weighted quantile sum (WQS) model consistently showed that Cu, Cr, Pb, and Cd ranked as the top four positive elements for ESCC risk. Multivariable logistic regression analysis indicated Pb and As were positively associated with tumor invasion (adjusted OR 3.024 [1.053-8.689]; OR 4.385 [1.271-15.126], respectively), whereas Se had the opposite trend (adjusted OR 0.261 [0.074-0.927). Patients with high Cr, Mn, or Pb showed worse overall survival (OS), and high Mn were linked to inferior progression-free survival (PFS) (all P < 0.05). Zn and Pb, and Mn and Cu were identified as independent prognostic factors for OS and PFS, respectively. This study suggests trace element disbalance in human body contributes to the risk of onset and progression of ESCC, especially in a high-incidence region. Further epidemiological and experimental studies were needed to clarify the probable pathogenic processes underpinning the potential link between trace element mixtures and ESCC.

Project description:Objective: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CRT) in multiple primary cancers (MPC) of the upper digestive tract in esophageal squamous cell carcinoma (ESCC). Methods: In a screening of 1193 consecutive patients diagnosed with ESCC and received radiotherapy, 53 patients presenting synchronous MPC in the upper digestive tract were retrospectively investigated. 53 consecutive patients with esophageal non-multiple primary cancer (NPC), matched by stage, age and sex, served as control. All of the patients received concurrent CRT. The median radiation dose was 60 Gy. Chemotherapy regimens were based on platinum and/or 5-fluorouracil. Clinical outcomes and treatment toxicities were compared. Results: Clinic-pathologic characteristics were well balanced between groups. MPC mostly located in esophagus (43, 81.8%), followed by hypopharynx (8, 15.1%) and stomach (2, 3.8%). In MPC and NPC patients, 94.3% and 96.2% completed the intended treatment. The immediate response rate was 73.6% vs 75.5%, with complete response rate of 11.3% vs 24.5% and partial response rate of 62.3% vs 51.0%. Two-year overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS) and distant progression-free survival (DPFS) were 52.2% vs 68.9% (p=0.026), 32.9% vs 54.0% (p=0.032), 60.8% vs 87.8% (p=0.002) and 64.0% vs 70.8% (p=0.22), respectively. Acute grade 3-4 toxicities were observed in 64.2% vs 54.7%, significantly higher in radiation esophagitis (49.1% vs 28.3%, p<0.001), and mucositis (11.3% vs 00p=0.027). Conclusions: Compared with matched NPC, ESCC accompanied with synchronous MPC was related to significantly impaired survival, elevated risk of locoregional disease progression and higher incidence of severe esophagitis and mucositis, following concurrent chemoradiotherapy. Future study on reasons for decreased efficacy of chemoradiotherapy will help to optimize treatment. Advanced radiation techniques may play a role in protecting normal tissues and reduce acute toxicities.

Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor diagnosis. Esophageal squamous dysplasia (ESD) is considered as an immediate precancerous lesion of ESCC. Lack of biomarkers for discriminating ESCC and ESD from healthy subjects limits the early diagnosis and treatment of ESCC. Therefore, a serum metabolomic strategy was conducted to identify and validate potential metabolic markers for the screening of ESCC and ESD subjects.MethodsA total of 74 patients with ESCC, 72 patients with ESD, and 75 normal control (NC) subjects were enrolled in this study. Gas chromatography-mass spectrometry was used to acquire serum metabolic profiles. Pathway analysis was conducted to uncover the fluctuated metabolic pathways during ESCC. Multivariate analyses were used to screen and validate the biomarkers.ResultsESCC, ESD, and NC subjects revealed progressively altered metabolic profiles, in which amino acids globally increased, while fatty acids decreased in ESCCs compared with the control groups. Pathway analysis demonstrated the activated biosynthesis of amino acids and inhibited desaturation of saturated fatty acids. The panel constructed with propanoic acid, linoleic acid, glycerol-3-phosphate, and l-glutamine showed the area under the curve (AUC), sensitivity, and specificity of 0.817, 0.75, and 0.74, respectively, in the discrimination of ESCC/ESD patients from NC subjects. The panel constructed by propanoic acid, l-leucine, and hydroxyproline revealed the AUC, sensitivity, and specificity of 0.819, 0.76, and 0.72, respectively, in the discrimination of ESD from NC subjects. The combination of hypoxanthine, 2-ketoisocaproic acid, l-glutamate, and l-aspartate showed the AUC, sensitivity, and specificity of 0.818, 0.83, and 0.74, respectively, in the discrimination of ESCC patients from ESD subjects.ConclusionsOur study revealed the systematic landscape for metabolic alterations in sera of ESD and ESCC patients. The defined metabolite markers showed reasonable performance in the discrimination of ESCC and ESD patients, and may provide helpful reference for clinicians and biologists.

Dataset Information

Association between Serum Level of Multiple Trace Elements and Esophageal Squamous Cell Carcinoma Risk: A Case-Control Study in China.

Publications

Association between Serum Level of Multiple Trace Elements and Esophageal Squamous Cell Carcinoma Risk: A Case-Control Study in China.

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