The Mediation Analysis Of C-reactive Protein In The Relationship Between Diet And Lung Cancer

Lung cancer is the leading cause of cancer death in the world.Therefore,it is necessary to take primary preventive measures for lung cancer as early as possible.Lung cancer preventionand is also an important way to reduce the burden of cancer.Many dietary factors,such as red meat,white meat,dietary fiber,and saturated fatty acids,are important targets for cancer prevention and affecting inflammatory pathways.Diet plays an important role in the occurrence and development of chronic inflammation.It plays not only direct role-providing nutrients and biologically active compounds that regulate inflammation,but also indirect role-affecting weight gain and obesity which were classic risk factors for systemic chronic inflammation.Chronic inflammation can promote the occurrence of cancer and participate in all stages of its occurrence and development,such as initiating cancer occurrence,promoting cancer development,and supporting cancer metastasis and spread.Therefore,chronic inflammation may play a mediating role in the effects of dietary factors on lung cancer.C-reactive protein is a sensitivity marker of chronic inflammation,and C-reactive protein is used as a surrogate indicator of chronic inflammation in this study.The graph model was constructed using the existing research results of C-reactive protein affecting HbAlc,C-reactive protein affecting sex hormone binding globulin(SHBG)and sex hormone,and HbAlc affecting SHBG and sex hormones.Then,we used difference method of mediation analysis based on Cox regression model to quantify the natural indirect effect of chronic inflammation in the relationship between diet and lung cancer in the subjects who met the exclusion criteria of the UK Biobank.Sequential causal mediation analysis was used to quantify the natural indirect effects of diet on lung cancer via C-reactive protein pathway,HbAlc pathway,sex hormone binding globulin pathway and sex hormone pathway,respectively.The aim is to provide evidence that chronic inflammation is a mediator in the relationship between diet and lung cancer,and to provide further supplement for the study on the pathogenesis of lung cancer.Results are as follows:1.After screening,288,480 individuals were included in this study cohort,containing 169,301 males and 119,179 demales.The baseline mean age was 58.19(7.35)years,the youngest was 38 years,and the oldest was 73 years.The median follow-up time was 8.95 years,and the longest follow-up time was 11.80 years.A total of 1842 people had lung cancer,the cumulative incidence was 6.39‰,among which 1107 men and 735 females had lung cancer,the cumulative incidences were 6.54‰ and 6.17‰,respectively.2.The older,the lower level of education or professional qualification certificate,the lower socioeconomic status,smoking and poor sleep quality,the higher incidence of lung cancer.The incidence of lung cancer was higher in those who ate processed meat,beef,mutton,pork and sdded salt to food(not include salt used in cooking).The incidence of lung cancer was lower in those who ate poultry meat,cereal,fruits and vegetables.3.The results of Cochran-Armitage Test for Trend indicated that there were certain trends between the levels of C-reactive protein,glycated hemoglobin,SHBG and the incidence of lung cancer.And with the increase of their levels,the incidence of lung cancer increased.4.After controlling for the influence of other factors,the total effect of diet on lung cancer indicated that eating processed meat,red meat,and salt added to food(not include salt used in cooking)can increase the risk of lung cancer and HR were 1.29(1.11,1.49),1.21(1.06,1.39)and 1.22(1.07,1.39),respectively.Eating white meat,cereals,fruits and vegetables can reduce the risk of lung cancer and HR were 0.79(0.60,1.03),0.53(0.32,0.88)and 0.71(0.60,0.83),respectively.5.After controlling for the influence of the four mediators(eg.CRP,HbAlc,SHBG and testosterone)and other factors,the natural direct effect of diet on lungcancer indicated that "eating processed meat≥1 time/week" without any of the above-mentioned mediation pathways can increase the risk of lung cancer by 24%(HR and 95%CI:1.24(1.07,1.44));"eating red meat≥1 time/week" can increase the risk by 18%(HR and 95%CI:1.18(1.03,1.35));"salt added to food(not include salt used in cooking)" can increase the risk by 17%(HR and 95%CI:1.17(1.03,1.33));"Eating white meat≥1 time/week" without any of the above-mentioned mediation pathways can reduce the risk of lung cancer by 17%(HR and 95%CI:0.83(0.63,1.09));"eating fruits and vegetables daily" can reduce the risk of lung cancer by 43%(HR and 95%CI:0.57(0.34,0.94));"eating cereals weekly" can reduce the risk by 26%(HR and 95%CI:0.74(0.63,0.87)).6.After controlling for the influence of other factors,the natural indirect effect through all intermediary pathways that the HR and 95%CI of "eating processed meat≥1 time/week" through all intermediary pathways was 1.036(1.022,1.050),which increased the risk of lung cancer by 3.6%;the HR and 95%CI of "eating fruits and vegetables daily" was 0.932(0.887,0.980),which reduced the risk of lung cancer by 6.8%.The natural indirect effects of other exposure factors through all intermediary pathways were similar."Eating processed meat≥1 time/week","eating red meat≥1 time/week",and "salt added to food(not include salt used in cooking)" can increase the risk of lung cancer.The indirect effects accounted for 14.09%,14.08%and 20.58%,respectively.Among them,the indirect effect of "salt added to food(not include salt used in cooking)" accounted for the largest proportion."Eating white meat≥1 time/week","eating fruits and vegetables daily" and "eating cereals weekly" can reduce the risk of lung cancer.The indirect effects accounted for 21.01%,11.16%,and 14.90%,respectively.Among them,the indirect effect of "eat white meat≥1 time/week"accounted for the largest proportion.7.After controlling for the influence of other factors,when analyzing the natural indirect effects of exposure factors on lung cancer via the CRP pathway,HbAlc pathway,SHBG and testosterone pathways,it is similar to the natural indirect effect through all intermediary pathways.Through the CRP pathway,the HR and 95%CI of"eating processed meat≥1 time/week" was 1.037(1.027,1.047),this increaseed the risk of lung cancer by 3.7%;the HR and 95%CI of "eating fruits and vegetables daily" was 0.962(0.921,1.000),the risk of lung cancer can be reduced by 3.8%.The natural indirect effects of other exposure factors via the CRP pathway,HbA1c pathway,and SHBG and testosterone pathways were similar,but the effects via the HbA1c pathway,SHBG and testosterone pathways were smaller than those via the CRP pathway.8.Cox regression analysis indicated that the risk of lung cancer increased with the increase in the number of dangerous exposures,and the total effect,natural direct effect and natural indirect effect were all the same.Natural indirect effects were mainly the indirect effects on lung cancer through the CRP chronic inflammation pathway.The natural direct effect of each exposure on lung cancer,natural indirect effect of each exposure on lung cancer,and the effect through the three pathways were brought back to the original data,the corresponding lung cancer risk was calculated for the subjects.According to the different risk factors contained in the study subjects,there were 64 risk types for all study subjects,of which 28,991(114 people had lung cancer)were not exposed to any of the above risks.The natural indirect effects of other risk types accounted for about 20%of the total effect,mainly the natural indirect effects on lung cancer through the CRP pathway.Conclusion:1.The effect of diet on lung cancer can be decomposed into natural direct effect and natural indirect effect,of which the natural direct effect accounts for about 80%,the natural indirect effect,accounting for about 20%.2.The natural indirect effect was mainly the natural indirect effects through the CRP pathway,and the natural indirect effects through the HbAlc pathway,SHBG and testosterone pathway were smaller than that through the CRP chronic inflammatory pathway.3.Whether the total effect,natural direct effect or natural indirect effect,high frequency of eating processed meat,red meat and salt added to food(not include salt used in cooking)can increase the risk of lung cancer.Eating white meat,cereals,fruits and vegetables can reduce the risk of lung cancer.4.The greater risk dietary factors,the greater natural indirect effect on lung cancer through the CRP inflammatory pathway.