| Objective Liver cancer is one of the most common malignancies in humans and has attracted much attention due to its high degree of malignancy,poor prognosis,and high mortality.The incidence of liver cancer in Guangxi is far higher than the national level.The occurrence of liver cancer is the result of multiple factors.Primary liver cancer(PLC)mainly includes hepatocellular carcinoma,intrahepatic cholangiocarcinoma,and hepatocellular carcinoma-intrahepatic cholangiocarcinoma.At present,the three major risk factors for the onset of liver cancer are aflatoxin intake,hepatitis B virus infection,and exposure to microcystins.In recent years,studies have shown that genetic susceptibility plays a role in the development of cancer,especially single nucleotide polymorphisms.Protein phosphatase 2A(PP2A)is a phosphoprotein phosphatase(PPP)family member commonly found in many organisms such as eukaryotes and yeasts.It belongs to the super family of protein serine/threonine phosphatases,and Phosphate was extracted from serine and threonine residues to reverse the role of protein kinases,which has a tumor suppressing effect and is involved in the development of tumors.This study intends to investigate the risk of liver cancer in terms of environmental factors,PP2A genes and gene-environment interactions through the study of cases and controls of primary liver cancer in Guangxi region,and helps to reveal the risk factors of liver cancer,the interaction of genes and environment,etc.,which will provide a scientific basis for prevention and treatment of liver cancer.Methods Using a case-control study,244 patients with primary liver cancer from the Affiliated Tumor Hospital of Guangxi Medical University were selected as the case group and 271 healthy persons from the Cancer Hospital were selected as the control group at the same time.Questionnaires were used to collect general demographic characteristics,past disease history,family history,smoking and drinking conditions,drinking water types,and dietary habits of the subjects.Peripheral venous blood of the subjects was collected for the extraction of genomic DNA.Matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)was used to detect the genotypes of the PP2A subunit genes rs10421191,rs11453459,rs1560092,rs7840855,rs10151527,rs1255722.Using SPSS 16.0 software to conduct statistical analysis of data.Theχ~2test was used to analyze the count data;the goodness-of-fitχ~2test was used to perform the Hardy-Weinberg genetic balance test of the control group;unconditional logistic regression was used to analyze the association of exposure factors and genotypes with the onset of primary liver cancer,trend test and gene-environment interactions.Power and Sample Size Program 3.0.5 was used to judge the power of the test.Linkage disequilibrium tests and Haplotype analysis were performed using Shesis online software.All tests were two-sided tests with P<0.05 being considered statistically significant.Results1.There was no significant difference in gender,age,and ethnic composition between the case group and the control group(P>0.05).Multivariate non-conditional logistic regression analysis of factors such as gender,age,ethnicity,education level and BMI showed that hepatitis B virus infection(OR=77.952,95%CI,35.839-169.550,P<0.001),family history of cancer(OR=2.980,95%CI,1.653-5.371,P<0.001),drinking water history of gutter and pond(OR=1.919,95%CI,1.024-3.595,P=0.042)and eating history of raw fish(OR=2.819,95%CI,1.786-4.451,P<0.001)were the main risk factors for primary liver cancer.However,the histories of smoking and drinking have nothing to do with the incidence of primary liver cancer.2.The frequency distribution of genotypes in the six SNPs were consistent with the Handy-weinberg equilibrium(P>0.05)in the control group.The genotype distribution of rs11453459 was significantly different between the case group and the control group(P<0.05).After adjusting for sex,age,ethnicity,education,BMI,history of hepatitis B virus infection,family history of cancer,and drinking history of ditch and pond water and eating history of raw fish,multivariate unconditional logistic regression analysis showed that rs11453459was associated with primary liver cancer[(GG)Vs.(-/-):adjusted OR=5.264,95%CI,1.630-17.005;(-/G)+(GG)Vs.(-/-):adjusted OR=2.086,95%CI,1.149-3.786;(GG)Vs.(-/-)+(-/G):adjusted OR=4.228,95%CI,1.357-13.174],and the locus genotype and association of risk of primary liver cancer with significant allele dose-response relationship(P=0.004).At the same time,the efficacy of the test was analyzed.When the bilateral statistics was at the level of 0.05 and the OR was 2.978,the power of rs11453459 variant genotype(GG)and primary liver cancer susceptibility was 79.9%.No significant association was found between the remaining sites and primary liver cancer(P>0.05).3.The results of stratified analysis of rs11453459 showed that in the subgroups with age>47 years old,Zhuang nationality,no history of hepatitis B virus infection,no family history of cancer,no drinking water in the ditch pond and no eating history of raw fish,codominant model,dominant model and recessive model significantly increased the risk of primary liver cancer(P<0.05).The results of interaction analysis showed that the genetic variation of rs11453459 was associated with gender,age,hepatitis B virus infection and eating history of raw fish in the pathogenesis of primary liver cancer(P<0.05).4.The linkage disequilibrium test results showed that the linkage disequilibrium between rs11453459 and rs10421191 and rs1560092 was positive(D’>0.5),and the linkage disequilibrium between rs11453459 and rs10421191was strongly positive(D’>0.8).Further haplotype analysis results showed that rs11453459,rs10421191,and rs1560092 included 5 types of haplotypes followed by(-)-A-G,(-)-A-T,(-)-G-G,(-)-G-T,G-G-T respectively,after exclusion frequency<0.03 haplotype.Among them,the distribution of G-G-T haplotype in the case-control group was statistically significant(OR=1.388,95%CI,1.024-1.881,P=0.034),suggesting that PPP2R1A haplotype G-G-T increases the risk of primary liver cancer.Conclusion1.The mutation of rs11453459 in PPP2R1A promoter region significantly increased the risk of primary liver cancer in Guangxi population,especially at the age of 47 years old,Zhuang nationality,no history of hepatitis B virus infection,no family history of cancer,drinking water without furrow pond water and no history of eating raw fish.2.PP2A rs11453459 gene polymorphism and environmental factors(age,history of hepatitis B virus infection,eating history of raw fish)have interactions and increase the risk of primary liver cancer.3.The G-G-T haplotype consisting of rs11453459,rs10421191 and rs1560092 of PPP2R1A gene may increase the risk of primary liver cancer. |
PDF Full Text Request