| Background:Hepatocellular carcinoma(HCC),short for liver Cancer,is one of the most common malignant tumors of the liver worldwide.According to Global Cancer Statistics 2020,liver Cancer is the third leading cause of cancer-related deaths worldwide.Liver Cancer has the 6th and 3rd highest incidence and mortality rates among cancers worldwide,and in China,the number of deaths due to liver cancer in2020 is 391,000,second only to lung cancer.Previous studies have shown that the development of liver Cancer is associated with several factors,including infection with hepatitis viruses(hepatitis B virus HBV,hepatitis C virus HCV),excessive smoking and alcohol consumption,consumption of foods containing aflatoxins,having cirrhotic disease and diabetes.In addition to the above common factors,genetic factors are also very important causes for the development of liver cancer.Single Nucleotide Polymorphisms(SNP)are the most abundant genetic variants associated with liver cancer.SNP are important forms of genetic variation in the human body,which are highly genetically stable and can alter the structure or expression of genes and thus their regulation of the body.Several studies have confirmed that SNP are one of the important causes of differences in organismal response to drugs or disease susceptibility.However,there are few studies on the correlation between hepatocellular carcinoma susceptibility and SNP,therefore,studies on the correlation between hepatocellular carcinoma susceptibility and SNP are important for the early diagnosis and treatment of hepatocellular carcinoma.Objective:To investigate the correlation between FGF1 rs34002 and PRKCE rs629772 SNP and hepatocellular carcinoma susceptibility in Yanbian region,and to provide a reliable theoretical basis for early screening of hepatocellular carcinoma high-risk population and discovery of new hepatocellular carcinoma susceptibility markers.Materials and methods:1.Research Subjects:A total of 470 patients diagnosed with liver cancer in Yanbian Hospital and Yanbian Cancer Hospital from2011 to 2017 were selected as the experimental group study subjects in this study,and470 healthy individuals who were examined in these two hospitals during the same period were randomly selected as the control group.2.Selection of Regulome-SNP:Firstly,the Regulome-SNP loci associated with HCC susceptibility were screened by the Regulome-DB database in the preliminary stage.Then,the NCBI-SNP database and Hapmap-SNP database were used to screen SNPs with minor allele frequency(MAF)>10%and linkage disequilibrium(LD)r~2<0.8 in the Chinese Han population,and their genes were confirmed by NCBI-SNP database.Next,a case-control study was performed to screen for Regulome-SNPs associated with HCC susceptibility(P<0.05).3.Extraction of DNA and genotyping:DNA was extracted from whole blood using a semi-automatic nucleic acid extractor Quick Gene-810(KURABO,Japan)and Quick Gene DNA whole blood kit S.The sample quality was determined after extraction of DNA from whole blood.PCR primers were designed to amplify DNA template fragments containing SNP loci,and single-base extension reactions were performed by specific primers,followed by SAP reactions and resin purification.Finally,the SNP loci were genotyped by Mass Spectrometry Analyzer.4.Statistical analysis:statistical analysis was performed using SPSS 26.0.The differences between the experimental and control groups in factors such as sex,age,ethnicity,smoking,alcohol consumption,and disease history and the frequency of genotype distribution were compared byX~2-test and t-test.The risk ratio(OR)of different SNP genotypes and HCC susceptibility were analyzed using a binary logistic regression model,and their 95%confidence intervals were calculated.Results:1.SNP genotype detection and peak map:Genotypes of SNP loci were detected by mass spectrometry analyzer,and genotype peak maps were obtained.2.Hardy-Weinberg genetic equilibrium test:The frequencies of genotype distribution between the experimental and control groups were analyzed by the goodness-of-fitX~2test and met the Hardy-Weinberg genetic equilibrium test(P>0.05).3.General information of study subjects:Statistical results showed that there was a significant difference between the experimental group and the control group in terms of drinking status,history of hepatitis and history of cirrhosis(P<0.05),but there was no significant no difference in terms of gender,age,ethnicity and smoking status(P>0.05).4.Relationship between SNP and PHC susceptibility:The results ofX~2tests showed that the differences in the distribution of the three genotypes of FGF1rs34002 between the experimental and control groups were not statistically significant(P>0.05),and the differences in the distribution of the three genotypes of PRKCE rs629772 between the experimental and control groups were statistically significant(P<0.05).Binary logistic regression analysis showed that the risk ratios for HCC in those carrying the FGF1 rs34002 TT and TG genotypes were 1.612 and 1.522(adjusted OR=1.612,95%CI=1.061-2.447,P=0.025;adjusted OR=1.522,95%CI=1.025-2.262,P=0.038),and a risk ratio of 1.415 for HCC for those carrying the PRKCE rs629772 TT genotype(adjusted OR=1.415,95%CI=1.089-1.839,P=0.009).5.Analysis of the number of risk genotypes and susceptibility to HCC:The number of risk genotypes was positively associated with HCC susceptibility,with those carrying 2 risk genotypes having a higher risk of HCC than non-carriers(adjusted OR=2.261,95%CI=1.333-3.833,P=0.002).Conclusion:FGF1 rs34002(T>G)and PRKCE rs629772(T>C)single nucleotide polymorphisms were significantly associated with hepatocellular carcinoma susceptibility in Yanbian,China,and those carrying FGF1 rs34002TT,TG and PRKCE rs629772TT genotypes had higher susceptibility to hepatocellular carcinoma. |
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