| BackgroundEsophageal cancer is a common tumor of the digestive tract.China is one of the regions with high incidence of esophageal cancer in the world,and the global data of esophageal cancer in 2020 showed that the number of incident cases was about 604,000 and the number of deaths was about 544,000.China accounts for 53.7% and 55.3% of all cases,respectively,of which esophageal squamous carcinoma accounts for 90.0% of all esophageal cancer pathological types.There are many factors in the development of esophageal squamous carcinoma,such as unhealthy lifestyle habits,dietary preferences,and harmful factors in the environment.In recent years,many studies have reported the association between trace elements and the risk of esophageal squamous carcinoma,but the overall effect of co-exposure to trace elements on the risk of esophageal carcinoma is not yet clear.ObjectivesThe aim of this study was to explore the association between trace element levels and the risk of esophageal cancer in samples from patients with esophageal squamous carcinoma and analyze the combined effect of these trace element exposures for esophageal cancer development and their interaction effects.Also,we investigate the correlation of trace element distribution between serum and whole blood to explore the clues of trace elements affecting esophaguscarcinogenesis.MethodsA case-control study design was used for this study.The case group was patients with esophageal squamous carcinoma and the control group consisted healthy individuals matched for age and sex to the case group;required demographic characteristics,serum and whole blood samples was collected from each group and additional tissue samples were collected from the case group.Inductively coupled plasma mass spectrometry was used to determine the levels of13 elements in the samples,including aluminum,vanadium,chromium,manganese,cobalt,nickel,copper,zinc,arsenic,selenium,strontium,cadmium,and lead.Differences in the ratios of the categorical variables(sex,smoking,alcohol consumption,family history of malignancy,BMI grouping,place of residence,etc.)were analyzed with the chi-square test or Fisher’s exact probability test,and differences between groups for continuous variables,such as age and element concentration,were analyzed using the Mann-Whitney U test;correlation analysis was performed using Spearman rank correlation Analysis coeffiecient.Logistic regression was used to establish single-and multi-factor regression models,and the ratio(OR)and confidence interval(95% CI)were calculated for each trace element;Bayesian kernel machine regression(BKMR)were used to investigate the joint effects and interaction effects of multiple trace element co-exposures on esophageal squamous carcinoma.Results1 A total of 191 control human and 185 new esophageal squamous carcinoma patients were included in this study,including 137 males and 54 females in the control group,with a median age of 65.0 years;133 males and 52 females in the case group,with a median age of 64.0years and an overall male to female sex ratio of 2.5:1.2 The concentrations of aluminum,manganese,cobalt,zinc,arsenic,selenium,strontium,and cadmium were significantly higher in serum samples from the control group than from the case group(P < 0.05);the opposite was true for vanadium.The differences in the concentrations of other trace elements between the two groups were not statistically significant.Multifactorial logistic regression analysis showed that the elements manganese,zinc,selenium and strontium were significantly negatively associated with the risk of esophageal squamous carcinoma(P <0.05);the opposite was true for vanadium and nickel.the results of BKMR showed that there was an interaction between the five elements of serum vanadium,nickel,zinc,selenium and strontium.3 In whole blood samples,the concentrations of vanadium,chromium,manganese,cobalt,nickel,zinc,arsenic,selenium and strontium were significantly higher in the control group than in the case group(P < 0.05);the opposite was true for copper and cadmium.The concentrations of aluminum,strontium and lead elements did not differ between the two groups.The results of multifactorial logistic regression showed a significant negative association between elemental concentrations of chromium,cobalt,zinc and selenium in whole blood and the risk of esophageal squamous carcinoma(P < 0.05);the opposite was true for copper.BKMR results did not reveal an interaction between the seven metals of vanadium,chromium,cobalt,nickel,copper,zinc and selenium in whole blood(P >0.05).4 In the comparison of esophageal tissues,the concentrations of manganese,selenium,and cadmium were statistically different among the three groups(P < 0.05);the elements manganese and selenium had the least abundant in the paracancerous tissuesas well as most abundant in the tumor tissues.The concentration of cadmium was distributed as the follow:normal tissues > paracancerous tissues > tumor tissues.levels of aluminum,zinc and lead have no difference between tumor tissues,paraneoplastic tissues and normal tissues(P >0.05).Five elements,vanadium,cobalt,nickel,arsenic and strontium,were found to be different in normal tissues compared with paraneoplastic tissues and tumor tissues,and their concentrations were distributed as normal tissues > paraneoplastic tissues > tumor tissues.Chromium was most abundant in the paraneoplastic tissue and least abundant in the tumor tissue;the distribution of copper was reversed.Analysis of normal and tumor tissues as two independent groups of samples showed differences in the concentrations of the nine elements(vanadium,chromium,manganese,cobalt,nickel,copper,selenium,strontium,and cadmium);the BKMR results showed that the combined effect of these nine trace elements and their interaction were not significant.5 In the correlation analysis between serum and whole blood,the elements cobalt,copper,arsenic,selenium and strontium have a certain degree of correlation.(P < 0.05).Conclusions1 There may be a positive association between high levels of serum vanadium and the risk of esophageal squamous carcinoma development;whereas zinc,selenium,and strontium may be protective factors against esophageal squamous carcinoma development.There may be a combined effect between nickel,zinc,selenium,and strontium.2 Copper may exhibit deleterious effects in whole blood of esophageal squamous carcinoma,and higher levels of whole blood chromium and cobalt may be negatively associated with the risk of esophageal squamous carcinoma.3 In esophageal tissues,the elements manganese and selenium may be enriched in cancerous tissues,while the elements vanadium,cobalt,nickel,strontium,and cadmium are the opposite;the combined effect of the above trace elements has not been found yet.4 There is a correlation between the elements in serum and whole blood samples,and the same element at different concentrations may play different roles at different sites. |
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