A Case-control Study On The Relationship Between Metal Exposure And The Risk Of Thyroid Cancer

ObjectiveThe pollution of metal elements in the environment is becoming more and more serious.Both heavy metal elements and essential trace elements will interfere with the normal function of the body’s endocrine system.To understand the exposure levels of 15 common metals in patients with Thyroid cancer（TC）,including magnesium（Mg）,cadmium（Cadmium,Cd）,chromium（Cr）,molybdenum（Molybdenum,Mo）,and zinc（Zinc,Zn）,iron（Iron,Fe）,arsenic（Arsenic,As）,barium（Barium,Ba）,cobalt（Cobalt,Co）,copper（Copper,Cu）,lithium（Lithium,Li）,manganese（Manganese,Mn）,lead（Lead,Pb）,selenium（Selenium,Se）,strontium（Strontium,Sr）,and further explore the effects of various metal element levels on the pathogenesis of TC.MethodsFrom August 2017 to October 2020,newly diagnosed patients with TC were collected from the First Affiliated Hospital of Anhui Medical University,the Second Affiliated Hospital of Anhui Medical University and Anhui Cancer Hospital of the First Affiliated Hospital of China University of science and Technology（West District）as case group.According to age,gender and permanent residence,newly admitted patients from non endocrine departments of the three hospitals were selected as control group.After obtaining the informed consent of the survey participants,questionnaire survey was conducted among all participants to obtain their general demographic characteristics,behavior habits,medical radiation exposure history,disease history,family history of disease and other information,and urine samples and fasting anticoagulant blood samples of all participants in the next morning were collected.ZEEnit700P graphite furnace atomic absorption spectrometer was used to determine the content of Cd in urine of all the investigated controls,Inductively Coupled Plasma-optical Emission Spectrometer（ICP-OES）was used to measure the concentrations of other 14 metal elements in urine.BECKMAN DXC800 ultraviolet spectrophotometer was used to measure the concentration of creatinine in urine to correct the concentration of metal elements in urine.Conditional logistic regression was used to conduct a multivariate analysis of the incidence of metal elements and TC.According to the quartiles of the 15 metal element exposure levels of the control population,the metal exposure levels of all the study populations were divided,and then the lowest quartile was taken as With reference,calculate the Odds Ratio（OR）and 95%Confidence Interval（CI）of each metal exposure level to the risk of TC.The Least Absolute Shrinkage and Selection Operator（LASSO）regression analysis was used to explore the multicollinearity and complex mixing effects among 15 metal elements.The metals selected by LASSO regression model were included in the multi-metal model for analysis.The Bayesian Kernel Machine Regression（BKMR）is used to further explore the mixed effects of several metal elements with joint effects.ResultsA total of 528 newly diagnosed TC patients and 528 controls were included in this study.The average age of the case group was 48.9 years old,and that of the control group was48.2 years old.There were 184 males and 344 females in both groups.The ratio of male to female was 1:1.9.After urine creatinine correction,the concentrations of CD,Cr,Mn and Pb in the patients with TC were significantly higher than those in the control group,while the contents of Ba,Co,Li and Sr in the patients with TC were significantly lower than those in the control group.Multivariate logistic regression analysis showed that in the single metal model,Cr exposure in the highest quantile increased the risk of TC.The corresponding OR and 95%CI were 1.57（1.06-2.32）.Mn exposure in the fourth quantile was associated with thyroid There was a positive association（OR=1.49,95%CI:1.03-2.15）.In addition,high exposure levels of Pb content could increase the risk of TC,with a hazard ratio of 1.60（95%CI:1.01-2.54）.Compared with the first quantile of Zn content,the highest quantile of Zn is negatively correlated with the risk of TC（OR=0.58,95%CI:0.37-0.94）,and the third and fourth quantiles of Co content are both related to the occurrence of TC.The risk is negatively correlated.For the essential trace element Se,the concentration levels of the second and third quantiles were significantly negatively correlated with the occurrence of TC(OR _{Q2 vs Q1}=0.63,95%CI:0.40-0.99;OR _{Q3 vs Q1}=0.56,95%CI:0.35-0.90).Seven metals,Zn,Cr,As,Cu,Li,Pb and Sr,were screened out by LASSO regression.The BKMR model was used to further explore the effect of combined exposure of metals on the pathogenesis of TC.The results showed that there was a potential joint effect of Cr and Pb on the pathogenesis of TC.When the other metals were in the median concentration,the higher the concentration of Cr in urine,the steeper the positive slope of Pb,and Li and Sr might also play an important role There is interaction.When the concentration of Li is at P25,the effect of Sr on the risk of TC increases.When the concentration of Li is at P75,the effect of Sr decreases.In the polymetallic model,we found that the fourth quantile of Cr exposure significantly increased the risk of TC（OR=2.80,95%CI:1.37-5.71）compared with the first quantile.Pb exposure in the highest quartile was positively correlated with the risk of TC,and the corresponding OR value was 2.46（95%CI:1.37-4.44）.The study also found that the highest concentration of Cu will reduce the risk of TC.The fourth quantile vs the first quantile:OR=0.36,95%CI:0.18-0.75,whether it is the second,third or fourth quantile of Li and Sr,will significantly reduce the risk of TC.ConclusionsThis study showed that the exposure level of metal elements in the population is high,and high exposure levels of Cr and Pb can significantly increase the risk of TC,while CO,Li and Sr may be protective factors of TC.There are complex joint exposures between metal elements,such as a certain synergistic effect between Cr and Pb,and low concentrations of Li can antagonize the protective effect of Sr on TC.