Correlation Between Peripheral Blood Bile Acid And Colorectal Cancer:A Retrospective Controlled Study

Background: Colorectal Cancer(CRC)is a common malignant tumor of digestive tract,which ranks second and third in global morbidity and mortality,and is still on the increasing trend in the world.The incidence of CRC is the result of a combination of genetic and environmental factors,including a family history of colon cancer,Familial adenomatous polyposis,advanced age,lack of exercise,high fat diet,obesity,diabetes,smoking and other risk factors.Clinical Studies and animal experiments have shown that high-fat Diet can increase the level of bile acid in the intestine,while the level of bile acid,especially secondary bile acid in the intestine of CRC patients is significantly higher than that of Control Group,it is suggested that intestinal bile acid is a risk factor for CRC.Some studies have shown that bile acid in the intestinal tract can act directly on the intestinal Mucosa epithelial cells,promote the development of colon cancer.Bile acid is an endogenous metabolic product of the body.It is also involved in the regulation of bile acid homeostasis and Lipid metabolism as a signal molecule.Some studies have found changes in peripheral blood bile acid levels in patients with CRC.However,because of the small sample size of these clinical studies,it is difficult to determine the relationship between peripheral blood bile acid levels and CRC.Objective: The aim of this study was to investigate the correlation between the level of total bile acid in peripheral blood and CRC.Methods: This is a retrospective,controlled study of 1,574 patients with CRC who underwent surgical resection and were diagnosed pathologically at Xijing Hospital between 1 January 2015 and 31 December 2019,compared with 1,594 patients with colorectal cancer who were hospitalized at the same time.The collected data information includes: Name,sex,age,nationality,blood type,BMI index and other General Information;Serum bile acid(TBA),total Bilirubin(TBIL),direct Bilirubin(DBIL),indirect Bilirubin(Ibil),glucose(Glu),γ-glutamine acyltransferase,uric acid(UA),Alkaline phosphatase,cholesterol(TC),triglyceride,high-density Lipoprotein,Low-density Lipoprotein,Tumor Markers(CEA,CA19-9,CA125,CA153,CA724,AFP,Afu),etc.Previous medical history such as history of biliary tract disease(cholecystectomy,gallstone,Gallbladder Polyp),history of appendectomy,history of CRC in First Degree relatives,history of diabetes,history of coronary heart disease,history of thyroid disease(hyperthyroidism,hypothyroidism),history of hypertension;History of use: Antidiabetic,antihypertensive,aspirin,clopidogrel,statins.For the case group,the location of tumor and TNM stage were also collected,and the postoperative survival was recorded by the surgical case follow-up system.T test and nonparametric test were used to analyze the serological data of the two groups,single factor analysis was used to analyze the risk factors of CRC,multiple factor analysis was used to analyze the Logistic regression model,and Kaplan-Meier method was used to analyze the survival rate.Results :(1)The TBA、ALP、GLU、CEA、CA153、CA125 level in the case group was higher than that in the control group(P< 0.05);(2)Single factor analysis showed that:male、between 58-75 years、Urban residents、group B blood、Occupation is physical and mental balance、ALP over 74.41IU/L、TBA over 15μmol/L、GLU over 5.26mmol/L、CEA over 2.29ng/mL、AFP over 2.75ng/mL、CA199 over 10.6ng/mL、CA125 over9.87ng/mL、Diabetes、aspirin、clopidogrel、antihypertensive drugs are CRC risk factors(P < 0.05);(3)Multivariate analysis showed that male,older than 57 years,urban residents,Occupation is physical and mental balance,antihypertensive drugs,clopidogrel,aspirin,TBA over 15μmol/L、ALP over 74.41IU/L、GLU over 5.26mmol/L、CEA over2.29ng/mL、CA199 over 10.6ng/mL、CA125 over 9.87ng/mL、were independent risk factors for colorectal cancer,The risk of colorectal cancer was negatively correlated with cholecystectomy.In addition,serum total bile acid levels in colorectal cancer patients were independent of tumor site,pathological stage,and patient survival.Conclusion: The level of bile acid in peripheral blood of CRC patients was significantly higher than that of non-colorectal cancer patients.Higher than 15 mol/l of bile acid in peripheral blood was an independent risk factor for CRC,suggesting that bile acid in peripheral blood was involved in the development of CRC.However,the relationship between peripheral blood bile acid level and intestinal bile acid level,and how peripheral blood bile acid affects the occurrence and development of CRC remain to be further explored.