| Prostate cancer is one of the most common malignant tumors in Male genitourinary system.At present, the incidence of prostate cancer is increasing in Chinese male year by year. Due to early symptoms of prostate cancer is not obvious, easy to delay early treatment of precious time.Human genome project have identified multiple genetic variants at 8q24 to be associated with PCa risk. This thesis explores its clinical prediction value and screening PCa high-risk groups test methods.This association was replicated in European Americans, African Americans, Native Hawaiians,Japanese, and Asian Indians.We performed this study to determine whether these two risk variants with rs1447295 and rs6983267 at 8q24 in European Americans were associated with PCa risk in Chinese Tianjin population,expectations for PCa in the early diagnosis of support.Purpose:We conducted a case-control study comprising of 40 prostate patients and 40 healthy controls to determine whether these two risk variants with rs1447295 and rs6983267 at 8q24 in European Americans were associated with PCa risk in Chinese Tianjin population.Genotyping by direct sequencing was performed for rs6983267 and rs1447295. Their genotype and allelictype association was also determined.Methods:1. Select SNP siteIn the homepage PUBMED bioinformatics NCBI database on manually prostate cancer SNPs related literature in the search box, find out relevant literature, record PCa closely related SNPs "rs" number. Finally after screening determine this topic research,prove prostate cancer is closely related to the two are located on the 8q24 with rs 1447295 and rs6983267 site.2. Research objectThis experimental samples derived from in February 2007～2009 during August the second hospital of Tianjin medical university urological department, including 40 cases China Tianjin area pathological diagnosised prostate cancer and 60 years or older men determined the healthy check-up of 40 patients with China tianjin area men's health'crowd from 2006～2008 in the second hospital of Tianjin medical university urology institute.3. The extraction of DNA samples40 cases of prostate cancer group were gathering EDTA anticlotting specimen, 40 control subjects were male healthy crowd separated from the separation of glue collected blood clot specimens, all specimens collected and extract DNA. Blood genomic DNA extracted with TIANGEN company DP318 kits (anticlotting), blood clots DNA extracted with TAKARA company DV811A kits.4. Obtain 2 SNP sites's DNA fragmentsFinally under the guidance of primer, after PCR we can get 2 SNP sites's DNA fragments.5. Direct sequencing method to SNP sites genotypeBy PCR SNP sites's DNA fragments were amplified by Shanghai Invitrogen PRISM experimental platform, the ABI ABI3730 platform applied gene type analyzer (i.e. DNA sequencing instrument) to directly sequence, analytic results have been arranged base sequence analysis, finally the output of Chromaslite 201 genotypes software will judge data results.6. Genotype and gene type of statistic treatment①For PCa group and control group rs6983267 and rs1447295SNP site were genotype frequency distribution Weinberg genetic balance tested.②For PCa group and control group rs6983267 and rs1447295SNP site's relevance for inspection were genotype and allele frequency X2 tested.③For PCa group and control group rs6983267 and rsl447295SNP site were assessed with PCa genotypes of degree.Above statistics were using statistical analysis software SPSS to statistical analysis (13.0 edition).Results:For PCa group and control group rs6983267 and rs1447295SNP site were genotyped and a chi-square test (X2 test) analysis allele frequency as the relevance of inspection to frequency (P=0.05) for significant Probability judgment standard and, OR(OR=1)was a value judgment for the relative risk analysis. Results are as follows:(1) For PCa group and control group rs1447295 SNP site have genotype and allele frequency X2 test analysis the relevance of inspection. (1) The PCa group and control group in rs1447295 SNP sites with CC genotypes, compared with AC genotype carriers have increased risk PCa significantly statistical significance, AC genotypes with PCa risks are carriers of the genotypes of CC 4.714 times, as carriers of the risk factors of aggressive prostate cancer (OR=4.714, P= 0.024, P<0.05).(2) Compared with CC genotypes, AA genotype carriers with PCa risk was not increased. (P=0.261, P>0.05)(3) Compared with CC genotypes, AC+AA genotypes with PCa risk no carrier increased. (P=0.117, P>0.05)(4) A allele frequency of rs1447295SNP site was higher than C allele frequency, but for the PCa group and control group A and C allele frequency have no significant differences, rs1447295A alleles carriers have no relevance with PCa (P=0.504, P> 0.05).(2) For PCa group and control group rs6983267SNP site have genotype and allele frequency X2 test analysis the relevance of inspection.(1) Compared with TT genotypes, GT genotype carriers with PCa risk was not increased. (P=0.679, P>0.05)(2)Compared with TT genotype, genotype GG increased risk of deeloping PCa carriers, and have significant statistical significance, genotype GG's PCa risks are 5.486 times of genotype TT carriers (OR=5.486,P=0.012,P<0.05).(3) Compared with TT genotypes, GT+GG genotype carriers will increase with PCa risk and statistical significance, GT+GG genotypes with PCa risks are 4.329 times of genotype TT (OR=4.329,P=0.012,P<0.05).(4) rs6983267SNP site's G allele frequency is higher than T allele frequency, and for PCa group and control group T and G crowd allele frequency was significant difference, rs6983267G alleles carriers and suffering from PCa have relevance, G alleles carriers is 2.251 times for T alleles carriers with PCa risk (OR=2.251,P=0.011, P<0.05), for aggressive prostate cancer risk factors.Conclusion:Two foreign coverage with PCa highly genes were linked rs6983267 and rs1447295 SNP sites in China, in Tianjin region with PCa between the crowd, as follows: (1) We only confirmed the rs 1447295 SNP sites in Chinese AC genotypes in Tianjin region with PCa crowd occurrence of relevance, (OR=4.714,P=0.024, P<0.05)A alleles and PCa had no relevance.(P=0.504, P>0.05)Results and reports in the literature less consistent. Reports in the literature, American white and black, Europe, and Japan rs1447295 SNP loci in the crowd of A alleles and PCa there were a close relationship.(2) We confirmed rs6983267SNP sites G alleles (OR=4.329, P=0.012, P<0.05) and GG genotype(OR=2.251, P=0.O11, P<0.05),GG and GT genotypes (OR=5.486, P=0.012, P<0.05) in Tianjin region in China in the crowd and PCa occurs with close relationship, results and reports in the literature to converge. Reports in the literature, American and European polish, and Japan the crowd with rs6983267SNP site G alleles there were significant PCa connection. |
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