The Effect Of The Energy Restriction On CRC Patients' Clinicopathological Features,Clinical Outcome And Relevant Mechanism

Background: Evidences have shown that exposure to the energy restriction at one's childhood is associated with a lower risk of developing colorectal cancer(CRC),and this changes have association with the epigenetic such as Cp G island methylator phenotype(CIMP).Also,some research shows that the mircobiota could influence the epigenetic dysregulations during the period of growth and development in our lives by some mechanism.Objective: In this study,we investigated the effect of the energy restriction on CRC patients' Clinicopathological features and clinical outcome,and we further explored theassociation of microbiota and risk of subsequent CRC characterized by the(promoter)Cp G island methylation phenotype(CIMP)when people experience energy restriction in early life?Method: we collected the tissues from the 1956-1964 who were experiencing the?Great Leap Forward Famine(GLFF)'and undergoing proctocolectomy with stages I–III cancer.60 sample from our patients were detected the BRAF mutation and the statue of Microsatellite Instability(MSI)and CIMP.Then,the samples from different patients were used 16 S r RNA gene sequencing approach and to determine differences in microbiota among tumor patient who experience the different period.We also use the Chi-square test to analysis the relationship between molecule change including the microsatellite instability(MSI,mismatch repair deficiency),Cp G island methylator phenotype(CIMP).We also used the Kaplan-Meier analysis as the method to assess the different between these three periods.And we want to know the change among these patients in three periodsResults: compare with different group,The different groups show the different in location of the CRC(P =0.034)and the CEA level(P =0.036).Also the patients who live in the different area show the different incidence rate(P=0.007).After we used the unvarible analysis by Kaplan-Meier,we found that the patients who experience the famine period has survival advantage than two other period(OS:68.8% vs 64.2%/62.1%).We also find Fusobacterium nucleatum,Bacteroides fragilis and Escherichia coli were more abundant in before and after famine group.We also found that the relationship between B.fragilis and BRAF mutation,while see the relationship between MSI and E.coli.Moreover,we could see the significant different in CIMP and MSI which compared the patients within F.nucleatum.Conclusions: Our study indicated that exposure to a severe energy restriction during childhood may induce changes of gut microbiota,which might affect the epigenetic expression and BRAF mutation and influence CRC patients' survival.