Evidence for a Rare Prostate Cancer–Susceptibility Locus at Chromosome 1p36

Abstract

Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.

Role of genetic polymorphisms of the RNASEL gene on familial prostate cancer risk in a Japanese population

“…Six prostate cancer susceptibility loci (HPC1 at 1q24-25 (Smith et al, 1996), PCAP at 1q42-43 (Berthon et al, 1998), HPCX at Xq27-28 (Xu et al, 1998), CAPB at 1p36 (Gibbs et al, 1999), HPC20 at 20q13 (Berry et al, 2000) and HPC2 at 17p12 (Tavtigian et al, 2001)) and two candidate susceptibility genes (HPC2/ELAC2 at 17q (Tavtigian et al, 2001) and RNASEL at 1q24-25 ) have been reported.…”

Familial risk of cancer by site and histopathology

“…In such studies, even verification of the tumor site has been problematic and reliable data on tumor characteristics cannot be obtained. [15][16][17][18][19] The Swedish Family-Cancer Database is unique in this regard because it includes a large proportion of the Swedish population in families starting from 1932 and identifies all cancers in the family members based on the nationwide Swedish Cancer Registry. The Swedish Family-Cancer Database has been updated several times, and familial risks have been published from various versions of it, though without histology-specific data, which will be reported here.…”

A missense substitution A49T in the steroid 5-alpha-reductase gene (SRD5A2) is not associated with prostate cancer in Finland

“…Recently, several loci have been implied in predisposing to prostate cancer by genetic linkage studies in cancer families. These include the HPC-1 locus at 1q24-q25 (Smith et al, 1996), HPC2 at 1q42-q43 (Berthon et al, 1998), HPCX at Xq27-q28 (Xu et al, 1998), HPBC at 1p36 (Gibbs et al, 1999), and loci at 20q13 (Berry et al, 2000), 11p (Gibbs et al, 2000) and 16q (Suarez et al, 2000). Exploration of the genetic basis of prostate cancer susceptibility by linkage analysis is challenging due to genetic heterogeneity (the large number of loci involved), due to incomplete penetrance of germline mutations and due to clustering of sporadic prostate cancer.…”