Correlation Between CYP27B1 And Vitamin D Receptor Gene Polymorphisms And Susceptibility To Colorectal Cancer,Clinicopathological Features And Biochemical Markers

Objective:Colorectal cancer?CRC?is a common malignant tumor of the digestive tract.The incidence and mortality of CRC in China are increasing year by year,becoming an increasingly prominent public health problem and social problem.Vitamin D is a protective factor for CRC and must be converted into active vitamin D?1,25-?OH?₂D₃?in the body to exert its physiological effects in combination with vitamin D receptor?VDR?.The gene encoding CYP27B1 of 1-?hydroxylase and VDR have obvious polymorphism,and its polymorphism can participate in the development of CRC by affecting gene expression and gene product structure and function.This study used a case-control study to investigate the relationship between CYP27B1 rs10877012,rs4646536 and VDR rs2228570,rs731236 and CRC susceptibility,and the relationship between CRC clinical pathological features and biochemical indicators,providing new ideas for the clinical diagnosis and treatment of CRC.Methods:303 CRC patients who had been admitted to the First Affiliated Hospital of China Medical University were selected as the case group and 286 patients with other age-sex matched other diseases were selected as the control group for case-control study from January to October 2018.The baseline data of the subjects were collected by questionnaire survey,including general demographic data and lifestyle habits survey;the clinicopathological data and biochemical indicators of CRC patients were obtained through the medical record inquiry system.The oral mucosal cells of the study subjects were collected with oral cotton swabs,and the sample DNA was extracted.The polymorphism of each gene was detected by primer-specific PCR amplification.The genotype and allele frequency distribution of each point in the case group and the control group were calculated and compared.The data were analyzed by Epidata 3.1 database,SPSS 20 for statistical analysis,t test,chi square test,rank sum test and Logistic regression and other statistical methods for data analysis and processing.Results:1.There were 303 cases in this study group?male:183 cases,female:120cases?,with an average age of 63.10±10.04 years,and 286 cases of the control group?male:164 cases,female:122 cases?,with an average age of 62.06±8.10 years old.There was no significant difference in age and gender between the two groups?P>0.05?.2.CRC common influencing factors screening results show that CRC family history,smoking,drinking,irregular diet,greasy diet are risk factors for CRC.3.rs10877012,rs4646536,rs2228570 genotype frequency distribution in line with Hardy-Weinberg equilibrium law.There was no significant difference in the distribution of rs10877012 genotype and allele frequency between the case group and the control group?P>0.05?.After age analysis,the rs10877012 in the age>60 years old group genotype distribution was associated with risk of CRC?P<0.05?.There was no significant difference in the distribution of rs4646536 genotypes and allele frequencies between the case group and the control group?P>0.05?.After stratification analysis by age and sex,the results showed that the case group and the control group genes were no significant difference in the frequency distribution of type and allele?P>0.05?.The distribution of rs2228570 genotype and allele frequency in the case group and the control group was statistically significant?P<0.05?;after stratified analysis by age and sex,in the population aged?60 years,rs2228570genotype and allele frequency distribution were associated with the risk of CRC?P<0.05?;in the female population,the genotype distribution of rs2228570 was associated with the risk of CRC?P<0.05?.There was a correlation between the genotype distribution of rs2228570 and TNM staging and differentiation?P<0.05?.The proportion of patients with M stage and tissue differentiation with poor differentiation and mucinous adenocarcinoma carrying CT genotype was higher.8.There was a correlation between the genotype distribution of rs2228570 and serum D-D levels.The serum D-D level of CRC patients with CT genotype was higher than that of CC genotype carriers,and the difference was statistically significant?P<0.05?.Conclusions:1.Family history of CRC,smoking,drinking,irregular diet,and greasy diet are risk factors for CRC.2.rs10877012 polymorphism was not associated with susceptibility to CRC,but may affect the risk of age>60 years old population;rs4646536 polymorphism was not associated with CRC susceptibility;rs2228570polymorphism was associated with susceptibility to CRC and may primarily affect the risk of?60 years of age and female population.3.The rs2228570 polymorphism was associated with clinical TNM stage and tissue differentiation in patients with CRC.4.The rs2228570 polymorphism was associated with serum D-D levels in CRC patients.