The Correlation Between Gene Polymorphismss Of ER Gene And Primary Liver Cancer

Estrogen receptors exist in estrogen target organs, some non estrogen target organs and malignant tumor cells in human body. Estrogen produces effect through combinations with ER. At present, occurrence mechanism of liver cancer has not been fully illuminated. Researches showed that human beings and livers of mammals contain estrogen receptors . It's a complex process of occurrence and development of tumors.Change of ERa expression levels and mutation and variation are related with occurrence and development of malignant tumors. Researches found that ER contained two hypotypes: ERa and ERβ. Nilsson M thought ER gene polymorphisms might lead to disproportion of gene in transcription and translation, and then ER was abnormal in expression and function.There are many polymorphisms sites in ERa gene upstream region, PvuII and XbaI restriction fragment length polymorphism enzyme slice sites had been definited and are located in 1 intron which includes enhanser,promotor important sequences. The point mutation may influence gene expression and function. There are T (thymine), A (adenine) repeated sequence in the upstream of ERa gene which belong to gene control region and control the gene expression.ERβgenes Polymorphic locus possessed 5'G1082A,3'UTR A1730G and No.5 intron had C(cytosine)and A(adenine) repeated polymorphism.The differences of its repeated frequency are connected with related diseases of estrogen levels.Our research on distribution of ER gene Polymorphism in primary liver cancer group and non liver diseases group aim to approach the relationship between ER gene Polymorphism and primary liver cancer from perspective molecule genetics.PART ONE THE STUDY ON THE RELATIONSHIP BETWEEN SINGLE NUCLEOTIDE POLYMORPHISMS OF THE ESTROGEN RECEPTOR GENE AND PRIMARY LIVER CANCERObjective: To investigate the relationship between polymorphisms of the estrogen receptor(ER) gene and primary liver cancer in Southwest region of China.Methods: 100 primary liver cancer patients(case group) and 100 no-hepatopathy person (control group) were recruited.They all came from Southwest of China. We observe the ERa gene PvuII and XbaI and ERβgene RsaⅠand AluⅠpolymorphisms'distribution in the two groups by polymerase chain reaction-restriction restriction fragment length polymo- rphisms(PCR-RFLP). In the meantime,the genotypes,allelotypes,haplotypes characters were analysed and the ERβgene polymorphisms were compared with patients'age. and gender.Results: PP, Pp, pp genotypic frequency differences were significant (χ2=14.963,P=0.001). P genotypic frequency in case group is 32.0%, and that in control group is 49.0%, the OR is 0.490(95%CI=0.326～0.735),P=0.001.X genotypic frequency in case group is 34.5%, that in control group is 20.5%, OR is 2.043(95%CI=1.302～3.205),P=0.002. RFLP of PvuII and XbaI in the 2 groups are distributed with polymorphisms. ppXx genetype constituent ratio was higher in case group(33%) than cotrol group(5%),but PPxx,Ppxx genetype constituent ratio was lower in case group(2%,22%)than cotrol group(9%,38%). It was not statistically significant different among diversity genotypes'age and gender.RR, Rr, rr genotypic frequency differences were not significant (χ2=11.379,P=0.003) in two groups. R allelotype frequency in case group was 35.0%, and that in control group was 51.0%, the OR was 0.517(95%CI=0.346～0.773),P=0.001.A allelotype frequency in case group was 20.5%, that in control group is 11.0%, OR was 2.086(95%CI=1.191～3.654),P=0.009. RsaI and AluI restriction fragment length polymorphism in the two groups showed no significant difference. There was not statistically significant different among diversity genotypes'age and gender in two groups.Conclusion: ERa,ERβgene polymorphisms is associated with primary liver cancer."X"allele may be a dangerous factor,"P"allele may be a beneficial factor for primary liver cancer."R"allele may be a protective factor for primary liver cancer,"A"allele may be a dangerous factor. The ppXx genetype may be the potential risk factors for primary liver cancer. The genetypes are not related to patients'age and gender in primary liver cancer.PART TWO THE ASSOCIATION OF REPEAT POLYMORPHISMS IN ER GENE WITH PRIMARY LIVER CANCERObjective: To investigate the association of dinucleotide repeat polymorphisms in ER gene with primary liver cancer.Methods: 100 primary liver cancer patients(case group) and 100 no-hepatopathy person(control group) were recruited. They all came from Southwest region of China. The (TA)n dinucleotide repeat in ERa gene upstream hypervariable region and (CA)n dinucleotide repeat in ERβgene the 5th exons loci hypervariable region were purifed,cloned and sequence analysed. we observed the ERa gene (TA)n and ERβgene(CA)n dinucleotide repeat polymorphisms distribution in two groups. In addition, the two kinds repeat polymorphisms were compared with patients'age and gender.Results: All samples exhibted 7 different alleles in ERa gene. The (TA)n dinucleotide repeats were 11～17.The distribution of the different alleles of the (TA)n dinucleotide repeat sequence in the case group and control group had significant difference(χ2=13.036,P=0.042).Fisher's exact test was applied to compare the frequency of each allele between two groups.The commonest allele was TA14. The frenquency of the TA13 allele was found to be significantly greater in primary liver cancer group(30%) than control group(14%)(P=0.006),OR=2.633 (1.296～5.347),and the frenquency of the TA15 allele was less in primary liver cancer group(18%) than control group(31%) (P=0.033),OR=0.489(0.252～0.948).All samples exhibted 9 different alleles in ERβgene. The (CA)n dinucleotide repeats were 16～24. There was not difference between distributing frequencies of CA repeat polymorphism in control and case groups (χ2= 9.554,P=0.298). SS genotype was defined as repeat number n≤20, LL for n>20. The SS genotypes rate were 66% in case group and 51% in control group respectively,OR=1.800(95%CI: 1.015～3.192). The SS and LL allele genotypes frequency were compared in two groups and the difference was significant (χ2=4.083,P=0.043). There were not statistically significant different among diversity allele genotypes′age and gender in primary liver cancer.Conclusion: The (TA)n and (CA)n dinucleotide repeat sequence in ERα,ERβgene which is associated with primary liver cancer. The ERαgene TA13 allele may be a risk factor; whereas ERαgene TA15 allele may be a protective factor for primary liver cancer. The ERβgene SS allele genotype may be the risk factor for primary liver cancer. The ERαgene TA allele and ERβgene CA allele genetypes are not related to patients'age and gender in primary liver cancer.