Inflammatory factors and prostate cancer:Two-sample Mendelian randomization analysis
Objective:To evaluate the potential causal relationship between inflammatory factors and PCa using the two-sample Mendelian randomization(MR)method.Methods:We selected summary statistics of genome-wide association studies(GWAS)(n=14 824)on 91 inflammatory factors,with PCa as the outcome in the latest 9th edition of FinnGen database for MR analysis.We evaluated the causal relationship between inflammatory factors and PCa using the odds ratio(OR)and 95%confidence interval(CI)of such regression models as inverse variance weighting(IVW),MR-Egger regression,simple mode(SM),weighted mode(WM)and weighted median estimator(WME),with IVW as the main statistical method for this study.We further verified the results of MR by Bayesian analysis,and evaluated the heterogeneity of genetic instrumental variables,pleiotropic effects and sensitivity of single nu-cleotide polymorphisms(SNP)as instrumental variables to the exposure-outcome relationship by Cochran's Q test,MR-Egger intercept test and leave-one-out cross validation.Results:IVW showed that among the 91 inflammatory factors,interleukin-22 receptor A1(IL-22RA1)and sulfotransferase 1A1(ST1A1)were correlated positively with the risk of PCa;IL-22RA1:IVW(OR[95%CI]:1.12[1.00-1.25],P=0.04);ST1A1:IVW(OR[95%CI]:1.08(1.00-1.16),P=0.03),while Chemokine ligand 11(CXCL11)and interleukin 17 A(IL-17 A)negatively with the risk of PCa;CXCL11:IVW(OR[95%CI]:0.88[0.81-0.95],P=0.00);IL-17A:IVW(OR[95%CI]:0.91[0.84-0.98],P=0.02).No potential horizontal pleiotropy was detected by MR-Egger intercept analysis(P>0.05,IL-22RA1=0.885,ST1A1=0.949,CXCL11=0.391,IL-17A=0.884),nor biased SNPs in the MR pleiotropy residual sum and outlier(MR-PRESSO)test(P>0.05,IL-22RA1=0.479,ST1A1=0.629,CXCL11=0.326,IL-17A=0.444),or heterogeneity P>0.05,IL-22RA1=0.543,ST1A1=0.677,CXCL11=0.336,IL-17A=0.494).Leave-one-out sensitivity analysis indicated no significant impact of individual SNP sites on the overall causal rela-tionship prediction,suggesting the reliable results of analysis.Conclusion:Among the 91 inflammatory factors,IL-22RA1 and ST1A1 have a positive causal relationship,while CXCL11 and IL-17A have a negative causal relationship with PCa.
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