Screening For Colorectal Cancer And Related Research On Colorectal Cancer Carcinogenesis Genes In Young People

Part OneOBJECTIVES:The sensitivity and specificity of the quantitative immunochemical fecal occult blood test(qFIT)for the detection of colorectal cancer(CRC)have been investigated in western countries.However,there is limited information about the performance of the qFIT in a Chinese population.In addition,few studies have been carried out to determine the association between the fecal hemoglobin(Hb)level and the location,size,and histological features of adenomas.METHODS:A total of 692 patients from three medical centers were enrolled in this study.They underwent a colonoscopy and provided stool samples.The fecal Hb level was measured in the stool samples using an OC-SENSA MICRO qFIT.The colonoscopy results,including the location,size,and histological features of the adenomas,as well as the relationship between the Hb level and different characteristics were analyzed.Moreover,the performance of the qFIT at various threshold Hb levels was evaluated.RESULTS:The colonoscopy results identified 76 patients with advanced colorectal neoplasia(ACRN).The sensitivity and specificity of qFIT for ACRN were 51.3%and 86.4%,at a fecal Hb level<400 ng/mL.The sensitivity and specificity for colorectal cancer were 61.0%and 89.1%,at a fecal Hb level<500 ng/mL.The fecal Hb level was influenced by the size and location of the adenoma.A large ACRN located on left side presented the highest Hb level.CONCLUSIONS:The qFIT has an acceptable sensitivity and specificity for ACRN detection.Furthermore,the qFIT results are associated with the location and size of the ACRN.Part TwoOBJECTIVES:The aim of this project is to develop and validate a risk score model to predict the risk of colorectal neoplasia.METHODS:This prospective and multi-centre study has enrolled 1010 participants to form the development set and collected their personal information about age,sex and so on.Then using multiple logistic regression to determine the relationship between risk factors and colorectal neoplasia.Finally we come out with a risk score model to predict the risk of colorectal neoplasia.To validate the model,we have collected a validation set of 175 participants.The sample scale will be enlarged later.RESULTS:In the derivation set,we formed a predictive model by risk factors:age,family history,diabetes,smoking and drinking.This score model can choose high risk people from average-risk population.Applying this model in validation set,in the AR group and in the HR group.CONCLUSIONS:The score model based on age,family history,diabetes,smoking and drinking is proved to be efficient in selecting high risk population before colorectal cancer screening.Part ThreeOBJECTIVES:To investigate if whole-exome sequencing can identify known or new mutation genes in early-onset CRC cases.To investigate the difference between early-onset CRC cases and elderly CRC cases.METHODS:Using data from Cosmic database,comparing the difference gene between early-onset CRC cases and elderly CRC cases.Then we performed whole-exome sequencing in 20 people for Peking union medical college hospital.10 from CRC patients diagnosed at ?40 years old.10 from patients diagnosed at>50 years old.Sequencing was performed on an Illumina Hiseq 2000 platform.Data were calculated to identify the difference gene mutation between these two groups.ResultsBy analysing Cosmic database,we have found 6 mutation gene:TNNB1,CNTN4,GLI3,BRAF,EPHA3,MSH2,which are different between early-onset CRC group and elderly CRC group with P value<0.01.Then we performed whole-exome sequencing in 20 people and formed similar results with the Cosmic database,except for Braf gene.Braf has higher mutation rate in early-onset CRC cases in our study but has the opposite result in the Cosmic database.In addition,we have found some different mutation gene which has higher mutation rate in early-onset group,such as SYNE1?RANBP2?MUC4?CCDC168?AHNAK2?ADGRV1 and soon.ConclusionsEarly-onset CRC cases have some different mutation gene with elderly group such as:TNNB1,CNTN4,GLI3,BRAF,EPHA3,MSH2,which indicates early-onset CRC cases may have some special gene in carcinogenesis.