Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease

Bao Li Chang, Sarah D. Isaacs, Kathy E. Wiley, Elizabeth M. Gillanders, S. Lilly Zheng, Deborah A. Meyers, Patrick Walsh, Jeffrey M. Trent, Jianfeng Xu, William B Isaacs

Research output: Contribution to journalArticle

Abstract

BACKGROUND. One of the difficulties confronting genetic studies of prostate cancer is the complex and heterogeneous etiology. Given the high population frequency of lesions meeting the histological definition of prostate cancer, a significant portion of men with a positive family history may be diagnosed due to increased surveillance and associated higher likelihood of biopsy. Over diagnosis decreases power to detect genes that increase susceptibility to a clinically significant prostate cancer. METHODS. We re-evaluated all 623 men with prostate cancer in our 188 hereditary prostate cancer families and identified a subset of 244 men with more aggressive disease based upon meeting at least one of the following clinical and/or pathologic criteria: tumor grade Gleason score >7, tumor stage T2c or higher, pretreatment PSA >20 ng/ml, rising PSA after treatment, evidence of metastasis, or death from prostate cancer. RESULTS. Genome-wide screens were re-performed by defining men as affected only if they met the criteria for clinically significant disease. The new analyses identified stronger evidence for linkage in Xq27-28 and 22q, as well as several novel loci, including 3p and 9p. CONCLUSIONS. Although, these results need to be confirmed in independent studies, our approach represents an important step to overcome the impact of over diagnosis in genetic studies of prostate cancer. Larger studies that incorporate this approach are needed.

Original languageEnglish (US)
Pages (from-to)356-361
Number of pages6
JournalProstate
Volume64
Issue number4
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Fingerprint

Neoplasm Genes
Prostatic Neoplasms
Genome
Neoplasm Grading
Neoplasms
Neoplasm Metastasis
Biopsy
Population
Genes

Keywords

  • Aggressive
  • Genome-wide scan
  • Hereditary
  • Linkage
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

Cite this

Chang, B. L., Isaacs, S. D., Wiley, K. E., Gillanders, E. M., Zheng, S. L., Meyers, D. A., ... Isaacs, W. B. (2005). Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease. Prostate, 64(4), 356-361. https://doi.org/10.1002/pros.20249

Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease. / Chang, Bao Li; Isaacs, Sarah D.; Wiley, Kathy E.; Gillanders, Elizabeth M.; Zheng, S. Lilly; Meyers, Deborah A.; Walsh, Patrick; Trent, Jeffrey M.; Xu, Jianfeng; Isaacs, William B.

In: Prostate, Vol. 64, No. 4, 01.09.2005, p. 356-361.

Research output: Contribution to journalArticle

Chang, BL, Isaacs, SD, Wiley, KE, Gillanders, EM, Zheng, SL, Meyers, DA, Walsh, P, Trent, JM, Xu, J & Isaacs, WB 2005, 'Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease', Prostate, vol. 64, no. 4, pp. 356-361. https://doi.org/10.1002/pros.20249
Chang BL, Isaacs SD, Wiley KE, Gillanders EM, Zheng SL, Meyers DA et al. Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease. Prostate. 2005 Sep 1;64(4):356-361. https://doi.org/10.1002/pros.20249
Chang, Bao Li ; Isaacs, Sarah D. ; Wiley, Kathy E. ; Gillanders, Elizabeth M. ; Zheng, S. Lilly ; Meyers, Deborah A. ; Walsh, Patrick ; Trent, Jeffrey M. ; Xu, Jianfeng ; Isaacs, William B. / Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease. In: Prostate. 2005 ; Vol. 64, No. 4. pp. 356-361.
@article{db131b236bae472eac80384fcd09b76c,
title = "Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease",
abstract = "BACKGROUND. One of the difficulties confronting genetic studies of prostate cancer is the complex and heterogeneous etiology. Given the high population frequency of lesions meeting the histological definition of prostate cancer, a significant portion of men with a positive family history may be diagnosed due to increased surveillance and associated higher likelihood of biopsy. Over diagnosis decreases power to detect genes that increase susceptibility to a clinically significant prostate cancer. METHODS. We re-evaluated all 623 men with prostate cancer in our 188 hereditary prostate cancer families and identified a subset of 244 men with more aggressive disease based upon meeting at least one of the following clinical and/or pathologic criteria: tumor grade Gleason score >7, tumor stage T2c or higher, pretreatment PSA >20 ng/ml, rising PSA after treatment, evidence of metastasis, or death from prostate cancer. RESULTS. Genome-wide screens were re-performed by defining men as affected only if they met the criteria for clinically significant disease. The new analyses identified stronger evidence for linkage in Xq27-28 and 22q, as well as several novel loci, including 3p and 9p. CONCLUSIONS. Although, these results need to be confirmed in independent studies, our approach represents an important step to overcome the impact of over diagnosis in genetic studies of prostate cancer. Larger studies that incorporate this approach are needed.",
keywords = "Aggressive, Genome-wide scan, Hereditary, Linkage, Prostate cancer",
author = "Chang, {Bao Li} and Isaacs, {Sarah D.} and Wiley, {Kathy E.} and Gillanders, {Elizabeth M.} and Zheng, {S. Lilly} and Meyers, {Deborah A.} and Patrick Walsh and Trent, {Jeffrey M.} and Jianfeng Xu and Isaacs, {William B}",
year = "2005",
month = "9",
day = "1",
doi = "10.1002/pros.20249",
language = "English (US)",
volume = "64",
pages = "356--361",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease

AU - Chang, Bao Li

AU - Isaacs, Sarah D.

AU - Wiley, Kathy E.

AU - Gillanders, Elizabeth M.

AU - Zheng, S. Lilly

AU - Meyers, Deborah A.

AU - Walsh, Patrick

AU - Trent, Jeffrey M.

AU - Xu, Jianfeng

AU - Isaacs, William B

PY - 2005/9/1

Y1 - 2005/9/1

N2 - BACKGROUND. One of the difficulties confronting genetic studies of prostate cancer is the complex and heterogeneous etiology. Given the high population frequency of lesions meeting the histological definition of prostate cancer, a significant portion of men with a positive family history may be diagnosed due to increased surveillance and associated higher likelihood of biopsy. Over diagnosis decreases power to detect genes that increase susceptibility to a clinically significant prostate cancer. METHODS. We re-evaluated all 623 men with prostate cancer in our 188 hereditary prostate cancer families and identified a subset of 244 men with more aggressive disease based upon meeting at least one of the following clinical and/or pathologic criteria: tumor grade Gleason score >7, tumor stage T2c or higher, pretreatment PSA >20 ng/ml, rising PSA after treatment, evidence of metastasis, or death from prostate cancer. RESULTS. Genome-wide screens were re-performed by defining men as affected only if they met the criteria for clinically significant disease. The new analyses identified stronger evidence for linkage in Xq27-28 and 22q, as well as several novel loci, including 3p and 9p. CONCLUSIONS. Although, these results need to be confirmed in independent studies, our approach represents an important step to overcome the impact of over diagnosis in genetic studies of prostate cancer. Larger studies that incorporate this approach are needed.

AB - BACKGROUND. One of the difficulties confronting genetic studies of prostate cancer is the complex and heterogeneous etiology. Given the high population frequency of lesions meeting the histological definition of prostate cancer, a significant portion of men with a positive family history may be diagnosed due to increased surveillance and associated higher likelihood of biopsy. Over diagnosis decreases power to detect genes that increase susceptibility to a clinically significant prostate cancer. METHODS. We re-evaluated all 623 men with prostate cancer in our 188 hereditary prostate cancer families and identified a subset of 244 men with more aggressive disease based upon meeting at least one of the following clinical and/or pathologic criteria: tumor grade Gleason score >7, tumor stage T2c or higher, pretreatment PSA >20 ng/ml, rising PSA after treatment, evidence of metastasis, or death from prostate cancer. RESULTS. Genome-wide screens were re-performed by defining men as affected only if they met the criteria for clinically significant disease. The new analyses identified stronger evidence for linkage in Xq27-28 and 22q, as well as several novel loci, including 3p and 9p. CONCLUSIONS. Although, these results need to be confirmed in independent studies, our approach represents an important step to overcome the impact of over diagnosis in genetic studies of prostate cancer. Larger studies that incorporate this approach are needed.

KW - Aggressive

KW - Genome-wide scan

KW - Hereditary

KW - Linkage

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=23944502116&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23944502116&partnerID=8YFLogxK

U2 - 10.1002/pros.20249

DO - 10.1002/pros.20249

M3 - Article

VL - 64

SP - 356

EP - 361

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 4

ER -