Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36

Mark Gibbs, Janet L. Stanford, Richard A. McIndoe, Gail P. Jarvik, Suzanne Kolb, Ellen L. Goode, Lisa Chakrabarti, Eugene F. Schuster, Valerie A. Buckley, Elizabeth L. Miller, Susan Brandzel, Sarah Li, Leroy Hood, Elaine A. Ostrander

Research output: Contribution to journalArticle

274 Scopus citations

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 (0) 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 0 = .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 0 = .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 0 = .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.

Original languageEnglish (US)
Pages (from-to)776-787
Number of pages12
JournalAmerican journal of human genetics
Volume64
Issue number3
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Gibbs, M., Stanford, J. L., McIndoe, R. A., Jarvik, G. P., Kolb, S., Goode, E. L., Chakrabarti, L., Schuster, E. F., Buckley, V. A., Miller, E. L., Brandzel, S., Li, S., Hood, L., & Ostrander, E. A. (1999). Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. American journal of human genetics, 64(3), 776-787. https://doi.org/10.1086/302287