The Association Of Polyphenol Intake With Gastric Cancer And Premalignant Lesions: A Cross-Sectional Population-Based Cohort Study

ObjectiveBased on the cross-sectional data of the Wuwei natural population cohort study,this study comprehensively analyzed the correlation between the intake of total polyphenols,total flavonoids,phenolic acids,lignans,stilbene,and other polyphenols,and the risk of gastric cancer（GC）and Premalignant lesions（PML）in Wuwei area.The purpose of this study is to provide an epidemiological basis for dietary factors and the risk of GC in the Wuwei area and to provide some nutritional references for dietary intervention in the prevention and treatment of GC.MethodsIn this study,through stratified cluster sampling,natural people aged 35-70 from9 pilot towns in Wuwei City of Gansu Province were selected to establish a research cohort.The epidemiological data,food frequency questionnaire（FFQ）survey,gastroscopy and pathological diagnosis data,and ¹⁴C-Urea Breath Test(¹⁴C-UBT)were collected through the whole population epidemiological questionnaire survey.Combined with searching the corresponding food polyphenols content in Phenol-Explorer Database,the semi-quantitative data in the questionnaire were transformed into quantitative data,and the dietary polyphenols data were integrated.Multivariate Logistic regression was used to analyze the correlation between total dietary polyphenols,sub-polyphenols,and GC and PML.PML includes Chronic atrophic gastritis（CAG）,Intestinal metaplasia（IM）and Low-grade intraepithelial dysplasia（LGD）.At the same time,the effects of different genders,Helicobacter pylori（Hp）infection status,and different food sources on the correlation between polyphenols and GC and PML were further analyzed.Results1.A total of 8507 people were enrolled in the study.Most of them were 40-60years old,54.2%of the participants were male,91.6%of the participants were farmers with a generally low level of education,60.7%of the participants never smoked,and95.4%of the participants did not drink alcohol.2.In the total population of the study,the medians of daily intake of total polyphenols,total flavonoids,phenolic acids,lignans,and other polyphenols were482.09mg/day,80.26mg/day,66.44mg/day,24.46mg/day and 7.11mg/day,respectively,while the daily intake of stilbene was deficient,only on 5.21ug/day.The total polyphenol intake was the highest in the LGD and CAG groups,the highest at489.43mg/day and 481.12mg/day,and the lowest in the GC group at 469.75mg/day.The distribution of other polyphenols intake was similar in each group.3.Multivariate logistic regression analysis of total polyphenols and subclass polyphenols intake with CAG,IM,LGD,and GC showed that stilbene intake was negatively correlated with IM risk（OR=0.96,P<0.05）;other polyphenols intake was negatively correlated in CAG,IM,LGD and GC groups,which respectively reduce the risk by 22%,53%,54%,and 65%,the protective effect had a dose-response relationship（P-trend<0.05）.There was a positive correlation between total polyphenols and LGD risk,OR=1.26,P=0.008;phenolic acid intake could increase LGD risk by 23%;total flavonoids and lignans intake did not correlate with PML and GC risk.4.The correlation analysis of total polyphenols and sub-polyphenols from different food sources with PML and GC showed that flavonoids,lignans,and stilbene from fruits had protective effects in PML and GC groups.In contrast,total polyphenols,Phenolic acids,and other polyphenols only had a defensive impact in the PML group.Phenolic acids and other polyphenols from staple food sources were protective factors for PML.Total polyphenols,flavonoids,phenolic acids,and lignans derived from fruit juices and vegetable juices had protective effects in IM and LGD groups;on the contrary,some food sources phenols increased the risk of disease,such as total polyphenols,flavonoids,Phenolic acids,and other polyphenols from vegetables were associated with increased risk of CAG,IM,and LGD.Total polyphenols,flavonoids,phenolic acids,lignans,stilbenes,and other polyphenols from chocolate and nuts were risk factors for PML,while total polyphenols and flavonoids from tea and coffee were risk factors for IM and LGD.5.Gender subgroup analysis showed that male intake of stilbene and other polyphenols decreased the risk of PML and GC,but total polyphenols and phenolic acids intake were associated with increased risk of PML and GC;female intake of other polyphenols was an independent protective factor for PML;in addition,the interaction test between total polyphenol intake and IM risk was 0.02,indicating that total polyphenol intake and risk reduction in the IM grouphad significantly different effects on men and women.6.The subgroup analysis of Hp showed that the intake of stilbene and other polyphenols was negatively correlated with the risk of PML and GC in Hp positive population,while in Hp hostile population,stilbene and other polyphenols intake was negatively associated with IM and LGD risk.In contrast,phenolic acid intake was positively correlated with LGD risk.The interaction test showed that the risk P value of other polyphenols intake and IM and LGD was less than 0.05,indicating that the protective effects of other polyphenols intake on IM and LGD may be different in different Hp infection states.Conclusion1.Other polyphenols intake was negatively correlated with PML and GC,stilbene intake was negatively correlated with IM risk,total polyphenols and phenolic acid intake were positively correlated with LGD,and no correlation was found between flavonoid and lignan polyphenols intake and disease risk in each group.2.Total polyphenols and sub-polyphenols from fruits,staple foods,fruit juices and vegetable juices may be negatively correlated with PML and GC risk,while polyphenols from vegetables,chocolate and nuts,tea and coffee may be positively correlated with PML risk,but no significant correlation with gastric cancer risk was found.3.There was no significant gender difference in the protective effects of stilbene and other polyphenols on PML and GC,but there was a gender difference in total polyphenols and the risk of IM,which only increased the risk of IM in men.4.Under different Hp infection conditions,other polyphenols were negatively correlated with the risk of PML and GC,and the protective effect of positive group was more significant than that of negative group.