Association Between Childhood Obesity And Adult Pancreatic Cancer Risk

Objective: Observational studies have shown that childhood obesity is positively correlated with the risk of pancreatic cancer in adults.But it is not clear whether this association is causal.Mendelian randomization is a method used to assess the causal relationship between risk factors and related outcomes.Two-sample Mendelian randomization is an extension of Mendelian randomization.It uses GWAS data to collect the associations between genotype and exposure and between genotype and results from two different databases.This study used a two-sample Mendelian randomization method to investigate whether the association between childhood obesity and adult pancreatic cancer risk is causal.Methods: This study used the Mendelian Randomization(2SMR)method of two samples to verify whether there is a causal association between childhood obesity and adult pancreatic cancer risk and the size of the association.Use 5 single nucleotide polymorphisms(SNPs)associated with childhood obesity as instrumental variables(IV)and use aggregated data from the GWAS genome-wide association study(from the MRBase platform)to conduct a 2SMR study to assess the causal association between childhood obesity and adult pancreatic cancer risk.All statistical analysis uses R software,which is a two-sided test,with P≤0.05 as the test level.The main effect indicators include beta,SE,P value,OR and 95% confidence interval(CI)of OR.Among them,the results are displayed in the form of statistical tables and forest plots according to the inverse variance weighting(IVW)model;the pleiotropic test is displayed in the form of statistical tables according to the MR-egger model;the quality control is based on the weighted median and maximum likelihood The method and weighted model are displayed in the form of scatter diagram and statistical table;the sensitivity analysis is displayed in the form of a leave-one-out method and in the form of a forest diagram;the final heterogeneity test is performed according to the MR-egger model and the IVW model and performed by the Q test verification.Results: According to the three assumptions of Mendelian randomization,rs4854344,rs571312,rs6752378,rs7138803,and rs9941349 were successfully selected as IVs.The results of the IVW model showed that childhood obesity is causally related to the risk of adult pancreatic cancer.The risk of adult pancreatic cancer increases by 0.363 times as the child’s BMI after natural log transformation increases by one unit(OR=1.363;95%CI=1.076-1.726;P=0.010).Conclusion: In short,childhood obesity is associated with an increased risk of pancreatic cancer in adults.This study provides evidence of a causal relationship between childhood obesity and adult pancreatic cancer risk.However,the results still need to be verified by large-scale intervention studies.