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

Am J Hum Genet. 1999 Mar;64(3):776-87. doi: 10.1086/302287.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alleles
  • Brain Neoplasms / genetics
  • Chromosomes, Human, Pair 1 / genetics*
  • Genetic Linkage
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Lod Score
  • Loss of Heterozygosity / genetics
  • Male
  • Middle Aged
  • Pedigree
  • Penetrance
  • Prostatic Neoplasms / genetics*

Substances

  • Genetic Markers