Fine-mapping the putative chromosome 17q21-22 prostate cancer susceptibility gene to a 10 cM region based on linkage analysis.
Prostate cancer linkage studies have suggested the existence of a prostate cancer susceptibility gene on chromosome 17q21-22. We now report the results of an extended linkage analysis including 95 new multiplex prostate cancer families and 9 additional microsatellite markers resulting in a maximum LOD score of 2.99 at approximately 81-82 cM for all 453 pedigrees. Results from these 95 new pedigrees provide additional support for a chromosome 17q21-22 prostate cancer susceptibility gene. Inclusion of the 9 additional markers significantly reduced the size of the candidate region, as defined using a 1-LOD support interval, especially when focusing analyses on subsets of pedigrees with four or more confirmed affecteds or average age of diagnosis less than or equal to 65 years. A novel subset analysis of only those families (n = 147) that had four or more prostate cancer cases and an average age of prostate cancer diagnosis < or = 65 years results in a maximum LOD score of 5.49 at 78 cM with a 1-LOD support interval of 10 cM. This large set of pedigrees with four more prostate cancer cases characterized by early-onset disease will serve as a useful resource for identifying the putative 17q21-22 prostate cancer susceptibility gene.
Lange
Ethan M
EM
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Robbins
Christiane M
CM
Gillanders
Elizabeth M
EM
Zheng
Siqun Lilly
SL
Xu
Jianfeng
J
Wang
Yunfei
Y
White
Kirsten A
KA
Chang
Bao-Li
BL
Ho
Lindsey A
LA
Trent
Jeffrey M
JM
Carpten
John D
JD
Isaacs
William B
WB
Cooney
Kathleen A
KA
D017668:Age of Onset; D000368:Aged; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics*