Evidence for a Prostate Cancer-Susceptibility Locus on Chromosome 20

Am J Hum Genet. 2000 Jul;67(1):82-91. doi: 10.1086/302994. Epub 2000 May 16.

Abstract

Recent studies suggest that hereditary prostate cancer is a complex disease involving multiple susceptibility genes and variable phenotypic expression. While conducting a genomewide search on 162 North American families with > or =3 members affected with prostate cancer (PRCA), we found evidence for linkage to chromosome 20q13 with two-point parametric LOD scores >1 at multiple sites, with the highest two-point LOD score of 2.69 for marker D20S196. The maximum multipoint NPL score for the entire data set was 3.02 (P=.002) at D20S887. On the basis of findings from previous reports, families were stratified by the presence (n=116) or absence (n=46) of male-to-male transmission, average age of diagnosis (<66 years, n=73; > or =66 years, n=89), and number of affected individuals (<5, n=101; > or =5, n=61) for further analysis. The strongest evidence of linkage was evident with the pedigrees having <5 family members affected with prostate cancer (multipoint NPL 3.22, P=.00079), a later average age of diagnosis (multipoint NPL 3.40, P=.0006), and no male-to-male transmission (multipoint NPL 3.94, P=.00007). The group of patients having all three of these characteristics (n=19) had a multipoint NPL score of 3.69 (P=.0001). These results demonstrate evidence for a PRCA susceptibility locus in a subset of families that is distinct from the groups more likely to be linked to previously identified loci.

Publication types

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

MeSH terms

  • Age of Onset
  • Aged
  • Alleles
  • Chromosome Mapping
  • Chromosomes, Human, Pair 20 / genetics*
  • Gene Frequency / genetics
  • Genes, Dominant / genetics
  • Genes, Recessive / genetics
  • Genetic Heterogeneity
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Lod Score
  • Male
  • Middle Aged
  • Models, Genetic
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / genetics*
  • Software
  • Statistics, Nonparametric

Substances

  • Genetic Markers