Genetic analysis of familial prostate cancer: Identification of a gene predisposing to prostate cancer (PCaP) on chromosome 1q 42.2-43.

Objectives : To conduct genetic linkage analysis in order to localize predi sposition genes for hereditary prostate cancer (CaP), as various epidemiolo gical studies have demonstrated a family aggregation in 15 to 25% of cases, and the development of hereditary forms in 5 to 10% of cases of CaP. Material and Methods : A genetic study on 47 French and German families inc luded 122 patients and 72 subjects considered to be healthy after PSA assay . This study was conducted by linkage analysis of 364 microsatellite marker s distributed throughout the genome (on average every 10 cM). Results : Parametric and nonparametric linkage analysis identified a locus on chromosome Iq 42.2-43, which could be with a gene predisposing to Cap (c alled PCaP). The primary site was confirmed by several markers, using 3 dif ferent genetic models. The maximum LOD score (probability of linkage betwee n the locus and the disease) on two-point analysis was 2.7 for the D1S2785 marker. Parametric and nonparametric multipoint analysis provided an HLOD s core and an NPL score of 2.2 and 3.1, respectively (with P=0.001). Heteroge neity analysis with calculations of LOD scores by multipoint analysis estim ated that up to 50% of hereditary Caps were related to this locus, with a h eterogeneity probability of 157/1. Analysis of a subgroup of 9/47 families characterized by early onset Cap (before the age of 60 years) confirmed the very high probability of localization of a predisposition gene at locus 1q 42.2-43 for these families (multipoint LOD score and NPL score of 3.31 and 3.32, respectively; with P=0.001). Conclusion : The identification of predisposition genes will eventually all ow identification within certain families of those subjects who have inheri ted the genetic abnormality and who therefore present a high risk of CaP. I t will then be possible to perform targeted screening of Cap in order to di agnose CaP as early as possible.