|Budget Amount *help
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥7,500,000 (Direct Cost: ¥7,500,000)
Involvement of genetic factors to prostate cancer development has long been proposed. Genetic analysis using large scale hereditary prostate cancer pedigrees has been reported from Western countries. Despite the effort to identify the high risk susceptibility gene associated with prostate cancer have been failed from those countries. In Japan, no reports have been published on genetic analysis of familial prostate cancer. In this study, we proposed the hypothesis that familial aggregation of prostate cancer was due to genetic polymorphisms of low risk genes. Many genes are involved in this category : androgen receptor, estrogen receptor, progesterone receptor, vitamin D receptor, GSTs,CYP 1A1,CYP17,CYP19,XRCC1,p53,PSA,UGT2B15,SRD5A,COMT,Cyclin D1,CDKNA1,IGFBP3,and so on. We analyzed genetic polymorphisms of these genes by PCR-RFLP,SSCP and direct sequencing methods.
We found that RNASEL Asp541Glu,HPC2 A1a541Thr,p53codon 72 Arg/Pro、CYP19 [TTTA]n、CyclinD1 A870G、CYP1A1 M1+M2, CDKNA1 C/T,IGFBP3 A/A, XRCC1 Arg399G1n、G S T p1,T1,M1,ER+CYP19+COMT,UGT2B15 D/Y,UGT2B15+CYP19 are associated with prostate cancer risk. These information would be helpful to identify the high risk group for prostate cancer development. Clinical stage was associated with RNASEL,p53,Cyclin D1,and CYP1A1 genotypes, whereas, pathological grade was associated with RNASEL,p53,IGFBP3,and CYP1A1 genotypes. These information would be helpful to identify the high risk group for prostate cancer development and to stratify the treatment options to prostate cancer.