The Association Between Nitrate Exposure And Cancer

Background Nitrate is a widespread contaminant of drinking water,but its potential health effects are unclear.In the body,nitrate is reduced to nitrite,which can react with amines and amides by nitrosation to form N-nitroso compounds,known animal carcinogens.N-nitroso compound formation is inhibited by certain nutrients,such as vitamin C,and increased by meat intake.Many articles have identified the sources of nitrate and its related compounds to be from water,food,cosmetics,tobacco,air and even from medication with both epidemiological studies and biological experiments of humans and animal experiments and several health issues or outcomes,even though some results have being contradictory.The aim of this study is to provide an all-round insight on global status of researches on the association between nitrate and related compounds and several health related issues which contributed to comprehending the academic status;and also to determine to what extent humans are at risk of getting cancer when exposed to nitrate and its related compounds.Methods Bibliometric analysis(1st part);A literature search was performed using the Web of Science Core Collection for Bibliometric analysis was from 1900-3rd March,2019 at 5:09 a.m.TXT File Merger(a Chinese software)was used to merger the articles(gotten in the plain text form),gotten from the same set of keywords.VOSviewer was used to analysis the keywords.For each the keywords that meets the threshold,the total strength of the occurrence links with other keywords was calculated.The quality of publications was assessed using total citations,citations per article,and Hirsh index(h-index).These parameters were used to assess quality of publications by journals,countries,most cited articles,and institutions.In addition to these parameters,impact factor(IF)was used as an indicator of journal strength publishing articles on nitrate and its related compounds – related health problems.Regarding the h-index and impact factor(IF),they were both obtained directly from Web of Science Core Collection.Systematic review(2nd part);A literature search was performed using the Web of Science Core Collection,Pub Med,Elsevier,Scopus,Cochrane library,WHO(Journal of Water and Health),Wiley Online Library,Research Gate,Oncotarget,Taylor & Francis online.Stata version 12.0(Stata Corp LP,College Station,TX,USA)was used to conduct meta-regression and meta-analysis(Of Binary and Continuous,(Effect/CI)).Meta-regression analysis was conducted to figure out the associations between nitrate and nitrite exposure and cancer risk,and recognize a positive metaregression coefficient(P ? 0.05).Meta-analysis was used to check the effect sizes(ORs(95 % CL))of the highest versus lowest category of dosage of nitrate and nitrite consumption from water and dietary intake for each type of cancer were meta-analyzed by comparing only extreme or highest categories of nitrate and nitrite consumption(highest versus lowest)first,and then by comparing all higher categories of nitrate and nitrite consumption,which were first pooled together using the random effect model and then secondly,compared to the lowest category(all other versus lowest).I2 statistics does not presented a notable heterogeneity(P?>?0.05 and I2???50%),Newcastle–Ottawa Quality Assessment Scale(NOS),was used to access the quality of included studies.Results Bibliometric analysis;In the analysis of keywords,there are trends(links)between nitrate,nitrite and its related compounds and cancer,methemoglobinemia,asthma,septic shock,birth defects and many other health issues.The analysis of keywords also strongly confirm that the sources of nitrate,nitrite and its related compounds were drinking water,food(dietary intake),tobacco,and air.USA,was the most productive country with highest number of documents published(1,570 articles).AMER HLTH FDN,is the institution which had the highest number of documents published(131 articles).Hecht,S.S.,is the author with highest number of documents published(115)related to this topic.Abstracts of Papers of the American Chemical Society,is the journal with highest number of documents published(124 articles).Oncology(812 articles)and Chemistry(787 articles)are the research fields with the have the highest number of articles published.From the top 100 articles published,“Role of N-Nitroso compounds(NOC)and N-nitrosation in Etiology of Gastric,Esophageal,Nasopharyngeal and Bladder cancer and contribution to Cancer of known exposure to NOC.”,is the article with highest number of citations(596 citations)”.Systematic review;A total of 82 articles were used for qualitative and quantitative analysis after proper selection.Meta-regression analysis showed there was an associations between nitrate and nitrite exposure from drinking water and stomach & gastric cancer(p = 0.000)and it was the opposite for ovarian cancer(p = 0.152).Meta-regression analysis showed there was an associations between nitrate and nitrite exposure from dietary intake and kidney cancer(p = 0.002),rectal cancer(p = 0.018),bladder cancer,(p = 0.021)and stomach & gastric cancer(p = 0.011).All other types of cancers didn't show any association.Meta-analysis showed there was an evidence of the association between the risk of brain cancer,cancer of other digestive organs,colon cancer,colorectal cancer and nitrate consumption in the analysis comparing the highest versus lowest category of dosage of nitrate consumption from drinking water,other types of cancers didn't show any association.There was an evidence of the association between the risk of non-Hodgkin's lymphoma,(OR = 1.08,95 CI: 1.01,1.14),colon cancer(OR =1.10,95 CI: 1.03,1.17),colorectal cancer,(OR=1.11,95 CI: 1.01,1.21)and nitrate consumption in the analysis comparing all combined higher dosages versus the lowest category of nitrate consumption from drinking water,other types of cancers didn't show any association.There was an evidence of the association between the risk of thyroid cancer(OR = 1.40,95 CI: 1.02,1.77)and nitrate consumption in the analysis comparing the highest versus lowest category of dosage of nitrate consumption from dietary intake,other types of cancers didn't show any association.There was no evidence of the association between the risk of any cancer and nitrate consumption in the analysis comparing all combined higher dosages versus the lowest category of nitrate consumption from dietary intake.There was no evidence of the association between the risk of any cancer and nitrite consumption in the analysis comparing the highest versus lowest category of dosage of nitrite consumption from dietary intake.There was an evidence of the association between the risk of glioma cancer(OR =1.13,95 CI: 1.03,1.22)and nitrite consumption in the analysis comparing all combined higher dosages versus the lowest category of nitrite consumption from dietary intake,other types of cancers didn't show any association.Conclusion The bibliometric analysis and systematic review showed that there are trends between nitrate and its related compounds and the risk of getting cancer and so many health issues in humans and animals.The systematic review also showed that with the increase intake of nitrate,nitrite and their related compounds from different sources over a long period of time,there is a higher chance or possibility of getting cancer and several other types' health issues.