Study On Risk Factors Of Colon Cancer Based On Umbrella Evaluation And Mendelian Randomization

Objective: The purpose of this study is to comprehensively evaluate the evidence reli ability of available colon cancer risk factors Meta analysis and Mendelian randomizati on study by umbrella evaluation method,and select the risk factors with low evidence reliability evaluation for Mendelian randomized study to verify the causal relationship with colon cancer.Methods: A comprehensive search of previously published Meta analysis of colon ca ncer risk factors and Mendelian randomized study was conducted to evaluate the credi bility of the evidence in the included literature by umbrella evaluation.Among them,t he Meta analysis uses the preset credibility evaluation criteria of evidence,and the Me ndelian randomization study carries on the descriptive evidence evaluation.The risk f actors with low or extremely low credibility of evidence in Meta analysis were screen ed and verified by Mendelian randomization method.In this study,acromegaly was se lected to study the causal relationship between acromegaly and colon cancer by Mend elian randomization.Mendelian randomization uses the large-scale GWAS data of acr omegaly,and according to the basic hypothesis of Mendelian randomization,four SN P significantly related to acromegaly are selected for two-sample Mendelian randomiz ed study.The analysis and mapping are carried out in R software.The inverse varianc e weighting method(IVW)and MR-Egger regression analysis are used to analyze the data.The results are presented in the form of scatter plot and statistical table.Quality control includes sensitivity analysis and heterogeneity test.Results: Through the umbrella evaluation,a total of 105 risk factors affecting the inci dence of colon cancer were included.The final results showed that the existing Meta a nalysis did not provide a highly reliable risk factor for colon cancer,and only one risk factor for colon cancer had a moderate credibility rating(cystic fibrosis).The credibili ty ratings of 8 risk factors for colon cancer were low(diabetes,total nut intake,total d ietary antioxidant capacity,time spent watching TV,occupational sedentary behavior,Barrett’s esophagus,metabolic syndrome(male),metabolic syndrome(female)).The10 risk factors for colon cancer were rated as extremely low(meat cooking by-product2-amino-3pyrum 4meme 8-trimethyl-3H-imidazol] quinoxaline(2-methylimidazo [4-methylimidazo] quinoxaline,Me IQx),meat-derived mutagenic activity(meatderived mutagenicactivity,MDM),meat cooking by-product 2-amino-3-methylimidazo [4-me thylimidazo] quinoxaline(2-amino-3-methylimidazo),meat cooking by-product 2-ami no-3-methylimidazo(4).8-trimethylimidazo,overweight,cruciferous vegetables,total dietary calcium,dietary vitamin D,acromegaly,DASH diet,non-fermented milk inta ke(male).22 risk factors had no significant effect on the incidence of colon cancer.T he study of 64 risk factors did not apply the credibility rating criteria of the evidence o f this study.The published Mendelian randomized study of risk factors for colon canc er only had a statistical validity of more than 80% for two risk factors,physical activit y and lifetime smoking.Acromegaly was selected as the exposure factor.Two samples of Mendelian randomization were used to study the causal relationship of colon cance r.The multiplicity test of tool variables showed that p=0.59.Three methods were used to estimate the causal effects.IVW analysis results showed that OR=1.00(0.94-1.07),p=0.99;MR-Egger analysis results showed that OR=0.94(0.77-1.15),p=0.61,Weight ed-Median analysis results showed that: OR=1.01(0.93-1.09),p=0.77.and the sensiti vity test shows that the confidence interval of the tool variable SNP passes through 0,indicating that the results of this Mendelian randomization study are relatively robust.The final results show that acromegaly is not an independent risk factor for colon canc er.Conclusion: At present,only a small number of risk factors for colon cancer have obt ained high credibility evidence.Patients with cystic fibrosis and lifelong smokers hav e a significantly higher risk of colon cancer,while people who take part in more physi cal activities have a significantly lower risk of colon cancer.Most of the research evid ence is less reliable.The risk factors of acromegaly with low credibility in umbrella e valuation were selected for Mendelian randomized study.It was found that acromegal y was not related to the incidence of colon cancer and was inconsistent with previous studies.Through this study,a comprehensive summary and analysis of the current col on cancer risk factors of Meta analysis and Mendelian randomization study,to clarify the evidence credibility of the existing colon cancer risk factors.It provides a certain g uiding significance for further research on risk factors of colon cancer.