Genetic analysis of prostate cancer : identification of susceptibility gene in 1p36 and 8p23 loci

点击翻译按钮获取中文摘要

We have studied the likage analysis of sib-pair of familial prostate cancer, and have found suggestive linkage in 1p36 and 8p23 loci. In this project, we further studied the association and functional studies of genes in these regions. One of the know susceptibility gene, macrophase scavenger receptor 1 (MSR1) contains seven missense mutations (Pro36Ala, Ser4lTyr, Val113Ala, Asp174Tyr, Pro275Ala, Gly369Ser, His441Arg) , one nonsense mutation (Arg293X), and 4 sequence variants in introns (PRO3, INDELI, IVS-59, INDEL7). In this study, we did not identified Pro36Ala, Ser41Tyr, Val113Ala, asp194Tyr, Gly369Ser, His441Arg, and IVS-59, however, we observed Lys338X, 3 mutation in promoter, 2 mutation in introns, 6 mutations in Exon 11. Association studied showed that G allele of PRO3 and presence of INDEL1 were significantly associated with prostate cancer risk. We further observed the significant association with rs26545629 of FDFT1 (farnesydiphosphate farnesyltransferase 1) and prostate cancer risk. Knock-down of FDFT1 gene expression led to the significant inhibition of prostate cancer cell proliferation in vitro. Thus, we observed the familial prostate cancer risk in some genes in 8p23 locus.