Genetic Epidemiology of Prostate Cancer

.........................................................................................................................6 Original papers ..............................................................................................................7 Abrevations....................................................................................................................8 Introduction ...................................................................................................................9 Incidence....................................................................................................................9 Risk factors ..............................................................................................................10 Diet ......................................................................................................................10 Hormonal and other factors .................................................................................10 Evidence of inherited susceptibility to prostate cancer ...........................................11 Case-control and cohort studies...........................................................................11 Twin studies.........................................................................................................11 Family-based segregation analyses .....................................................................12 Definition of hereditary prostate cancer ..............................................................14 Malignancies associated with HPC .........................................................................14 Gene mapping..........................................................................................................16 Human genetics and recombination.....................................................................16 Linkage analysis ..................................................................................................16 Linkage analyses of prostate cancer ........................................................................18 Prostate cancer susceptibility genes.........................................................................20 RNASEL..............................................................................................................20 MSR1...................................................................................................................21 HPC2/ELAC2......................................................................................................22 Other candidate genes..............................................................................................22 Aims.............................................................................................................................24 Material and methods ..................................................................................................25 HPC families ascertained for linkage analysis (Paper I, II, and IV)........................25 Patients with prostate cancer and controls (Paper III) .............................................26 Cohort of relatives of patients affected with HPC (Paper IV).................................27 Genotyping ..............................................................................................................28 Genome-wide markers (Paper I and IV)..............................................................28 Markers at 8p22-23 (Paper II) .............................................................................28 Sequence variants of the RNASEL gene (Paper III) ...........................................28 Statistical analysis....................................................................................................30 Linkage analysis (Paper I, II and IV)...................................................................30 Test for HWE (Paper III).....................................................................................31 Association analysis (Paper III)...........................................................................31 Haplotype analysis (Paper III) .............................................................................31