Telomere length as a risk factor for hereditary prostate cancer

Lauren M. Hurwitz, Christopher M Heaphy, Corinne E. Joshu, William B Isaacs, Yuko Konishi, Angelo Michael Demarzo, Sally D. Isaacs, Kathy E. Wiley, Elizabeth A Platz, Alan Keith Meeker

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Telomeres are repetitive nucleotide sequences that stabilize the ends of chromosomes. Critically short telomeres are thought to contribute to cancer development by increasing chromosomal instability. We hypothesized that shorter leukocyte telomere length, a surrogate for inherited prostate cell telomere length, would be associated with increased risk of prostate cancer in hereditary prostate cancer (HPC) families. METHODS: One hundred twelve affected and 63 unaffected men from 28 families were drawn from the Johns Hopkins HPC family database. Relative mean telomere length was measured in isolated peripheral leukocyte DNA by quantitative PCR. Conditional logistic regression was used to estimate the association between quartile of age-adjusted telomere length and prostate cancer. RESULTS: Men in the shortest quartile of telomere length did not have increased odds of prostate cancer compared to men in the other three quartiles (OR=0.84, 95% CI: 0.32-2.20, P=0.73). However, when the analysis was restricted to affected men with blood drawn before or within a year of diagnosis (N= 39) and all unaffected men, shorter telomere length was moderately associated with increased odds of prostate cancer (OR=3.55, 95% CI: 0.82-15.43, P=0.09). CONCLUSIONS: Though we found no association overall, shorter leukocyte telomere length may be associated with increased odds of prostate cancer when measured in pre-diagnostic samples. Further prospective research is warranted exploring the utility of telomere length as a prostate cancer biomarker. Prostate 74:359-364, 2014.

Original languageEnglish (US)
Pages (from-to)359-364
Number of pages6
JournalProstate
Volume74
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Telomere
Prostatic Neoplasms
Leukocytes
Prostate
Familial Prostate cancer
Chromosomal Instability
Nucleic Acid Repetitive Sequences
Tumor Biomarkers
Chromosomes
Logistic Models
Databases
Polymerase Chain Reaction
DNA

Keywords

  • HPC families
  • Prostate cancer risk
  • Telomere biology

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Telomere length as a risk factor for hereditary prostate cancer. / Hurwitz, Lauren M.; Heaphy, Christopher M; Joshu, Corinne E.; Isaacs, William B; Konishi, Yuko; Demarzo, Angelo Michael; Isaacs, Sally D.; Wiley, Kathy E.; Platz, Elizabeth A; Meeker, Alan Keith.

In: Prostate, Vol. 74, No. 4, 2014, p. 359-364.

Research output: Contribution to journalArticle

@article{553d026e9f984de0b476940b600d0625,
title = "Telomere length as a risk factor for hereditary prostate cancer",
abstract = "BACKGROUND: Telomeres are repetitive nucleotide sequences that stabilize the ends of chromosomes. Critically short telomeres are thought to contribute to cancer development by increasing chromosomal instability. We hypothesized that shorter leukocyte telomere length, a surrogate for inherited prostate cell telomere length, would be associated with increased risk of prostate cancer in hereditary prostate cancer (HPC) families. METHODS: One hundred twelve affected and 63 unaffected men from 28 families were drawn from the Johns Hopkins HPC family database. Relative mean telomere length was measured in isolated peripheral leukocyte DNA by quantitative PCR. Conditional logistic regression was used to estimate the association between quartile of age-adjusted telomere length and prostate cancer. RESULTS: Men in the shortest quartile of telomere length did not have increased odds of prostate cancer compared to men in the other three quartiles (OR=0.84, 95{\%} CI: 0.32-2.20, P=0.73). However, when the analysis was restricted to affected men with blood drawn before or within a year of diagnosis (N= 39) and all unaffected men, shorter telomere length was moderately associated with increased odds of prostate cancer (OR=3.55, 95{\%} CI: 0.82-15.43, P=0.09). CONCLUSIONS: Though we found no association overall, shorter leukocyte telomere length may be associated with increased odds of prostate cancer when measured in pre-diagnostic samples. Further prospective research is warranted exploring the utility of telomere length as a prostate cancer biomarker. Prostate 74:359-364, 2014.",
keywords = "HPC families, Prostate cancer risk, Telomere biology",
author = "Hurwitz, {Lauren M.} and Heaphy, {Christopher M} and Joshu, {Corinne E.} and Isaacs, {William B} and Yuko Konishi and Demarzo, {Angelo Michael} and Isaacs, {Sally D.} and Wiley, {Kathy E.} and Platz, {Elizabeth A} and Meeker, {Alan Keith}",
year = "2014",
doi = "10.1002/pros.22755",
language = "English (US)",
volume = "74",
pages = "359--364",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Telomere length as a risk factor for hereditary prostate cancer

AU - Hurwitz, Lauren M.

AU - Heaphy, Christopher M

AU - Joshu, Corinne E.

AU - Isaacs, William B

AU - Konishi, Yuko

AU - Demarzo, Angelo Michael

AU - Isaacs, Sally D.

AU - Wiley, Kathy E.

AU - Platz, Elizabeth A

AU - Meeker, Alan Keith

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Telomeres are repetitive nucleotide sequences that stabilize the ends of chromosomes. Critically short telomeres are thought to contribute to cancer development by increasing chromosomal instability. We hypothesized that shorter leukocyte telomere length, a surrogate for inherited prostate cell telomere length, would be associated with increased risk of prostate cancer in hereditary prostate cancer (HPC) families. METHODS: One hundred twelve affected and 63 unaffected men from 28 families were drawn from the Johns Hopkins HPC family database. Relative mean telomere length was measured in isolated peripheral leukocyte DNA by quantitative PCR. Conditional logistic regression was used to estimate the association between quartile of age-adjusted telomere length and prostate cancer. RESULTS: Men in the shortest quartile of telomere length did not have increased odds of prostate cancer compared to men in the other three quartiles (OR=0.84, 95% CI: 0.32-2.20, P=0.73). However, when the analysis was restricted to affected men with blood drawn before or within a year of diagnosis (N= 39) and all unaffected men, shorter telomere length was moderately associated with increased odds of prostate cancer (OR=3.55, 95% CI: 0.82-15.43, P=0.09). CONCLUSIONS: Though we found no association overall, shorter leukocyte telomere length may be associated with increased odds of prostate cancer when measured in pre-diagnostic samples. Further prospective research is warranted exploring the utility of telomere length as a prostate cancer biomarker. Prostate 74:359-364, 2014.

AB - BACKGROUND: Telomeres are repetitive nucleotide sequences that stabilize the ends of chromosomes. Critically short telomeres are thought to contribute to cancer development by increasing chromosomal instability. We hypothesized that shorter leukocyte telomere length, a surrogate for inherited prostate cell telomere length, would be associated with increased risk of prostate cancer in hereditary prostate cancer (HPC) families. METHODS: One hundred twelve affected and 63 unaffected men from 28 families were drawn from the Johns Hopkins HPC family database. Relative mean telomere length was measured in isolated peripheral leukocyte DNA by quantitative PCR. Conditional logistic regression was used to estimate the association between quartile of age-adjusted telomere length and prostate cancer. RESULTS: Men in the shortest quartile of telomere length did not have increased odds of prostate cancer compared to men in the other three quartiles (OR=0.84, 95% CI: 0.32-2.20, P=0.73). However, when the analysis was restricted to affected men with blood drawn before or within a year of diagnosis (N= 39) and all unaffected men, shorter telomere length was moderately associated with increased odds of prostate cancer (OR=3.55, 95% CI: 0.82-15.43, P=0.09). CONCLUSIONS: Though we found no association overall, shorter leukocyte telomere length may be associated with increased odds of prostate cancer when measured in pre-diagnostic samples. Further prospective research is warranted exploring the utility of telomere length as a prostate cancer biomarker. Prostate 74:359-364, 2014.

KW - HPC families

KW - Prostate cancer risk

KW - Telomere biology

UR - http://www.scopus.com/inward/record.url?scp=84895918194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895918194&partnerID=8YFLogxK

U2 - 10.1002/pros.22755

DO - 10.1002/pros.22755

M3 - Article

VL - 74

SP - 359

EP - 364

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 4

ER -