The Association Between Polymorphisms In HPGD Genes And Prostate Cancer Risk In Chinese Population

PurposeProstate cancer?PCa?is frequently diagnosed malignant tumor among men worldwide and becomes a first major public health concern in the United States.The incidence of prostate cancer was not high in China,but recently,it has been increased,especially in the developed areas.According to statistics,the incidence of prostate cancer in Shanghai from5.6/100,000 in 1999 rose to 12.96/10 million in 2009,the incidence of the Beijing is also increasingly close to the developed countries.Prostate cancer patients usually progress slowly and have a long-term of survival.In some cases,their tumors develop very rapidly and need for early active intervention.So far,however,the molecular genetics factors of occurrence and progression in prostate cancer has not yet fully understood.To explore the molecular mechanism of the development of prostate cancer is very important.The exact pathogenesis and progression mechanisms of prostate cancer have not yet been fully elucidated,but the currently recognized susceptibility factors are genetic,environmental,dietary and ethnic factors.In recent years,the relationship between single nucleotide polymorphisms?SNPs?and prostate cancer has become a hotspot.SNP refers to the DNA sequence polymorphism caused by a single nucleotide variation at the genome level of the chromosome,with a single base conversion,transversion,insertion and deletion.15-hydroxy-prostaglandin dehydrogenase?15-PGDH?is a key enzyme for prostaglandin degradation,which affects the occurrence and development of tumors by affecting the degradation of prostaglandin E₂.SNP?rs8752?is located in the3'untranslated region?UTR?of HPGD gene.The relationship between SNP?rs8752?and colon cancer,breast cancer has been confirmed.However,the detailed role of 15-hydroxyprostaglandin dehydrogenase?HPGD?,the key enzyme degrading prostaglandin E₂,remains unclear in prostate cancer.Materials and MethodsA total of 109 patients that underwent prostate needle biopsy were included in a hospital-based case control research model.All patients were divided into two groups according to the pathologic diagnosis of prostate biopsy.54 patients who were diagnosed with prostate cancer was included in group one while group two contains 55 benign prostatic hyperplasia?BPH?patients as control.For prostate cancer group,subjects are divided into groups by Gleason score pathological stage.3ml peripheral vein blood each person was collected,peripheral blood genome DNA were extracted,after PCR amplification the gene fragment of HPGD Gene,SNP?rs8752?loci would be sequencing by direct sequencing.At last use statistics method to find the relationship between the gene and prostate cancer.Results1.The frequency of the GG homozygote and AG+GG genotype were 37.74%and62.26%in the patient group,while these values were 62.50%and 37.50%in the control group.Compared with the GG genotype,the combined GA+AA genotypes has a significantly higher risk of prostate cancer?OR=2.750;95%CI:1.266-5.971,P=0.011?.2.Furthermore,the risk effect was obtained in subgroups of PCa patient group,the AA+AG genotypes significantly increased the Gleason score?AA+AG vs GG:OR=3.50,95%CI=1.106-11.072,P=0.033?and the risk of clinical stage?AA+AG vs GG:OR=3.44,95%CI=1.068-11.068,P=0.038?.Conclusions1.SNP?rs8752?of HPGD gene was found to be responsible for the susceptibility to prostate cancer in Chinese individuals.2.In patients with prostate cancer,the SNP?rs8752?loci of the HPGD gene is associated with the Gleason score of tumor.3.In patients with prostate cancer,the SNP?rs8752?loci of the HPGD gene is associated with the clinical stage of tumor.4.In patients with prostate cancer,HPGD gene SNP?rs8752?loci associated with the prognosis of prostate cancer.